Efficacy and Safety of Metronomic Capecitabine in Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Metronomic capecitabine has been found to be useful in several types of cancers such as pancreatic cancer, breast cancer, gastrointestinal cancers, nasopharyngeal carcinoma, and metastatic colorectal cancer. This unique systematic literature review and meta-analysis was undertaken to assess the effectiveness and safety of metronomic capecitabine as a treatment regimen for hepatocellular carcinoma. METHOD: A systematic search of major databases was performed. Eight studies that dealt with the use of metronomic capecitabine for hepatocellular carcinoma (HCC) were selected, seven were non-randomized control trials (n-RCTs), and one was a randomized control trial (RCT). Meta-analysis of these studies was performed using Review Manager v5.3 and STATA 15.1 software. The pooled prevalence of overall survival (OS), progression-free survival (PFS), overall response rate (ORR), grade 1-2 adverse events (grade 1-2 AEs), grade 3-4 adverse events (grade 3-4 AEs) was determined, including publication bias and sensitivity analysis. RESULT: Eight studies met the inclusion criteria, combining the pooled data of 476 patients from safety and efficacy studies. The pooled prevalence of disease control rate (DCR) and overall response rate (ORR) achieved with metronomic capecitabine was 36% (95% CI 32-41) and 7% (95% CI 5-9) respectively. The median progression-free survival (PFS) and median overall survival (OS) were 3.57 months (95% CI 3.29-3.85) and 11.75 months (95% CI 10.56-12.95) respectively. The incidence of grade 3-4 adverse events (grade 3-4 AEs) and grade 1-2 adverse events (grade 1-2 AEs) was 38% (95% CI 32-44) and 73% (95% CI 67-79) respectively. CONCLUSION: This meta-analysis highlights metronomic capecitabine as a potential treatment for hepatocellular carcinoma (HCC) in the advanced stage. However, effective management of capecitabine's side effects is essential.

Study on Effects of Sublingual Immunotherapy in Allergic Rhinitis Patients.

Allergic Rhinitis is one of the most common allergic disease and characterized by sneezing, rhinorrhea, nasal congestion and nasopharyngeal itching. The initial management includes pharmacological treatment and the patients who are refractory to pharmacological treatment are then reffered for immunotherapy. SLIT has been widely used for treatment of allergic rhinitis and has proven its clinical efficacy. The objective of the present study was to assess the clinical effects, safety and tolerability of sublingual immunotherapy (SLIT) among the patients suffering from allergic rhinitis. The study was conducted from Aug 2018 to April 2021 and 40 patients with convincing history, positive skin prick test to one or more allergen extracts were recruited. SLIT was conducted with antigens (mix), namely dust mites, tree pollens, grass pollens and weed pollens in patients of allergic rhinitis for 1 year. There was significant improvement in quality of life and symptoms severity(Nasal and Non-Nasal) from base line to end of 1 year. SLIT lowers the total IgE, absolute eosinophilic count and medication requirement. Sublingual Immunotherapy for specific allergens decreases clinical symptoms in patients with allergic rhinitis and sensitivity to multiple allergen.

Laryngotracheal Stenosis: Our Experience in a Tertiary Care Hospital.

Laryngotracheal stenosis is a recalcitrant disease with high morbidity. Laryngotracheal stenosis can be defined as a partial or circumferential narrowing of the airway and may be congenital or acquired. Sites involved are supraglottis, glottis, or sub glottis. The goal of treating the patient with laryngotracheal stenosis is to reconstruct an adequate airway while preserving phonation and airway protection. Furthermore, there is no fixed treatment for laryngotracheal stenosis, the choice of surgical procedure is determined by the individual anatomy, involved site, length and luminal narrowing of stenotic segment and function of the larynx and trachea, together with patient factors and available facilities. To determine the most common aetiology of laryngotracheal stenosis and to study outcome of various treatment modalities and their efficacies according to the site of stenosis and time of presentation. We have prospectively studied 25 cases of laryngotracheal stenosis who presented in Department of ENT, Civil Hospital, Ahmedabad from May 2019 to December 2021. All patients with clinical suspicion of laryngotracheal stenosis underwent CECT Neck and Thorax with virtual bronchoscopy, flexible bronchoscopy and graded according to myer cotton classification and then included in study. In our study of 25 patients 19 patients had history of intubation. Out of 25 patients, 5 Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation patients had supraglottic stenosis, 14 had subglottic stenosis and 6 patients had tracheal stenosis. 20 patients were tracheostomised. Bilateral vocal cord mobility is pre requisite for any surgical intervention and for decannulation of tracheostomy tube. Laser ablation is best modality for supra glottis stenosis patients. Treatment options of subglottic and tracheal stenosis patients depends on vocal cord mobility, % of luminal narrowing and type of stenosis on flexible bronchoscopy and CT scan. Patients of subglottic or tracheal stenosis having Myer cotton grading 1 or 2 were successfully treated by Laser + Balloon dilatation while grade 3 or 4 by resection and end to end anastomosis. Endoscopic CO2 laser ablation with/without balloon dilatation gives promising results in cases of supra glottic stenosis and in soft, mucosal, short segment (< 1.5 cm), grade 1 or 2 stenosis patients with subglottic or tracheal stenosis. In patients with subglottic or tracheal stenosis having hard, cartilage framework involvement, > 1.5 cm stenotic segment, Grade 3 or 4 needed external open approach like tracheal resection and end to end anastomosis.

An Unusual Case of Parapharyngeal Desmoid Fibromatosis - A Rare Case Report.

Desmoid fibromatosis (DF) is a rare locally aggressive, connective tissue malignancy developing in musculoaponeurotic tissues with an incidence of 2-4 per million population. We presented a case of a 3-year-old patient with a left parapharyngeal mass, histopathological examination suggesting DF, who underwent complete surgical excision without recurrence or requirement of cardiac resynchronization therapy.

Different Approaches for Thyroid Surgery.

Introduction: Surgery remains main treatment of choice for thyroid nodule for diagnosis and treatment. Conventional thyroid surgery gives scar in the neck so many young patients particularly unmarried females demand thyroid surgery without visible scar in the neck for cosmetic reason. Extra cervical approaches have continued to evolve with an increasing body of research (Sarda AK, Bal S, Kapoor MM (1989) Near-total thyroidectomy for carcinoma of thyroid. Br J surg 76(90):2).majority of them presenting in 21-30 age So, here there is evaluation of minimally invasive or endoscopic thyroid techniques. Here, we have studied endoscopic approach and utilize it to minimize scar and scarless thyroid surgery. Aims and objectives: To evaluate optimal patient selection criteria. To study various surgical approaches and outcomes. To decide surgical approach according to size. To study patients satisfaction. Methodology: It was a prospective study of 50 patients with a duration of 3 years. All the Euthyroid cases with clinically palpable thyroid swelling in age group 15-60, after a detailed clinical history and examination, who required surgery and concern for visible neck scar are councelled and included in our study. Results: In our study 45 patients were females and 5 were males with majority of them presenting in 21-30 age group. All the patients in our study are presented with neck swelling. In most patients FNAC is suggestive of colloid goiter. Conclusion: Endoscopic thyroid surgery is mainly indicated for young patients having benign thyroid tumor less than 3 cm in size. Transaxillary and retroauricular are common approaches and is selected as per patient choice and surgeon expertise. Transaxillary thyroidectomy can be performed safely as conventional thyroidectomy.

Comparative evaluation of early versus late tracheostomy for reduction of the length of ICU stay, incidence of nosocomial pneumonias, risk of laryngeal injury and mortality of mechanically ventilated patients at a Tertiary Care Hospital in Western India.

Introduction: Tracheostomy is a very common procedure performed in ICU as it offers significant advantages over prolonged endotracheal intubation. It facilitates weaning by decreasing the work of breathing in patients with limited reserve by decreasing the dead space area, decreases the requirement for sedation, and may allow for earlier patient mobilization, feeding, and physical and occupational therapy as compared to prolonged intubation along with lesser oral and oropharyngeal ulcerations, improves pulmonary toileting, and lowers incidence of pulmonary infections. Tracheostomy, however, is not devoid of risks. Complications may include hemorrhage, stoma infections and granulations, pneumothorax, subcutaneous emphysema, tracheal stenosis, tracheomalacia, and rarely death. Hence, performance of tracheostomy should be considerate to outweigh benefit-risk ratio. Aims and objectives: To evaluate the early versus late tracheostomy for reduction of the length of ICU stay, incidence of nosocomial pneumonias, risk of laryngeal injury and mortality of mechanically ventilated patients. Materials and methods: We conducted a retrospective study from May, 2019 to April, 2021 of patients being tracheostomized in medical ICU at Civil Hospital, Ahmedabad, who were previously intubated endotracheally and were on mechanical ventilation. The decision to tracheostomize would be taken by physicians in their routine rounds in ICU. Results: Incidence of endolaryngeal complications like laryngotracheal stenosis, stomal granulations, fistula as well as nosocomial infections have lower incidence in early tracheostomy as compared to with late. Mortality remains same in both the groups as well as hospital and ICU stay.

Comparison of Heart Team vs Interventional Cardiologist Recommendations for the Treatment of Patients With Multivessel Coronary Artery Disease.

Importance: Although the heart team approach is recommended in revascularization guidelines, the frequency with which heart team decisions differ from those of the original treating interventional cardiologist is unknown. Objective: To examine the difference in decisions between the heart team and the original treating interventional cardiologist for the treatment of patients with multivessel coronary artery disease. Design, Setting, and Participants: In this cross-sectional study, 245 consecutive patients with multivessel coronary artery disease were recruited from 1 high-volume tertiary care referral center (185 patients were enrolled through a screening process, and 60 patients were retrospectively enrolled from the center's database). A total of 237 patients were included in the final virtual heart team analysis. Treatment decisions (which comprised coronary artery bypass grafting, percutaneous coronary intervention, and medication therapy) were made by the original treating interventional cardiologists between March 15, 2012, and October 20, 2014. These decisions were then compared with pooled-majority treatment decisions made by 8 blinded heart teams using structured online case presentations between October 1, 2017, and October 15, 2018. The randomized members of the heart teams comprised experts from 3 domains, with each team containing 1 noninvasive cardiologist, 1 interventional cardiologist, and 1 cardiovascular surgeon. Cases in which all 3 of the heart team members disagreed and cases in which procedural discordance occurred (eg, 2 members chose coronary artery bypass grafting and 1 member chose percutaneous coronary intervention) were discussed in a face-to-face heart team review in October 2018 to obtain pooled-majority decisions. Data were analyzed from May 6, 2019, to April 22, 2020. Main Outcomes and Measures: The Cohen κ coefficient between the treatment recommendation from the heart team and the treatment recommendation from the original treating interventional cardiologist. Results: Among 234 of 237 patients (98.7%) in the analysis for whom complete data were available, the mean (SD) age was 67.8 (10.9) years; 176 patients (75.2%) were male, and 191 patients (81.4%) had stenosis in 3 epicardial coronary vessels. A total of 71 differences (30.3%; 95% CI, 24.5%-36.7%) in treatment decisions between the heart team and the original treating interventional cardiologist occurred, with a Cohen κ of 0.478 (95% CI, 0.336-0.540; P = .006). The heart team decision was more frequently unanimous when it was concordant with the decision of the original treating interventional cardiologist (109 of 163 cases [66.9%]) compared with when it was discordant (28 of 71 cases [39.4%]; P < .001). When the heart team agreed with the original treatment decision, there was more agreement between the heart team interventional cardiologist and the original treating interventional cardiologist (138 of 163 cases [84.7%]) compared with when the heart team disagreed with the original treatment decision (14 of 71 cases [19.7%]); P < .001). Those with an original treatment of coronary artery bypass grafting, percutaneous coronary intervention, and medication therapy, 32 of 148 patients [22.3%], 32 of 71 patients [45.1%], and 6 of 15 patients [40.0%], respectively, received a different treatment recommendation from the heart team than the original treating interventional cardiologist; the difference across the 3 groups was statistically significant (P = .002). Conclusions and Relevance: The heart team's recommended treatment for patients with multivessel coronary artery disease differed from that of the original treating interventional cardiologist in up to 30% of cases. This subset of cases was associated with a lower frequency of unanimous decisions within the heart team and less concordance between the interventional cardiologists; discordance was more frequent when percutaneous coronary intervention or medication therapy were considered. Further research is needed to evaluate whether heart team decisions are associated with improvements in outcomes and, if so, how to identify patients for whom the heart team approach would be beneficial.

Should dual antiplatelet therapy be used in patients following coronary artery bypass surgery? A meta-analysis of randomized controlled trials.

BACKGROUND: We assessed the effectiveness of dual antiplatelet therapy (DAPT) post elective or urgent (i.e., post acute coronary syndrome [ACS]) coronary artery bypass graft surgery (CABG). METHODS: We systematically searched MEDLINE, EMBASE, and the Cochrane Registry from inception to August 2015. Randomized controlled trials (RCTs) in adults undergoing CABG comparing either dual vs. single antiplatelet therapy or higher- vs. lower-intensity DAPT were identified. RESULTS: Nine RCTs (n = 4,887) with up to 1y follow-up were included. Five RCTs enrolled patients post-elective CABG (n = 986). Two multi-centre RCTs enrolled ACS patients who subsequently underwent CABG (n = 2,155). These 7 RCTs compared clopidogrel plus aspirin to aspirin alone. Two other multi-centre RCTs reported on ACS patients who subsequently underwent CABG comparing higher intensity DAPT with either ticagrelor (n = 1,261) or prasugrel (n = 485) plus aspirin to clopidogrel plus aspirin. Post-operative anti-platelet therapy was started when chest tube bleeding was no longer significant, typically within 24-48 h. There were no differences in all-cause mortality in clopidogrel plus aspirin vs. aspirin RCTs; conversely, all-cause mortality was significantly lower in ticagrelor and prasugrel vs. clopidogrel RCTs (risk ratio[RR] 0.49, 95% confidence interval[CI] 0.33-0.71, p = 0.0002; 2 RCTs, n = 1695; I(2) = 0%; interaction p < 0.01 compared to clopidogrel plus aspirin vs aspirin RCTs). There were no differences in myocardial infarctions, strokes, or composite outcomes. Overall, major bleeding was not significantly increased (RR 1.31, 95% CI 0.81-2.10, p = 0.27; 7 RCTs, n = 4500). There was heterogeneity (I(2) = 42%) due almost entirely to higher bleeding reported for the prasugrel RCT which included mainly CABG-related major bleeding (RR 3.15, 95% CI 1.45-6.87, p = 0.004; 1 RCT, n = 437). CONCLUSIONS: Most RCT data for DAPT post CABG is derived from subgroups of ACS patients in DAPT RCTs requiring CABG who resume DAPT post-operatively. Limited RCT data with heterogeneous trial designs suggest that higher intensity (prasugrel or ticagrelor) but not lower intensity (clopidogrel) DAPT is associated with an approximate 50% lower mortality in ACS patients who underwent CABG based on post-randomization subsets from single RCTs. Large prospective RCTs evaluating the use of DAPT post-CABG are warranted to provide more definitive guidance for clinicians.

Colchicine in cardiac disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Colchicine has unique anti-inflammatory properties that may be beneficial in various cardiovascular conditions. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines this issue. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Database from inception to June 2014 for RCTs using colchicine in adult patients with cardiac diseases. Results were pooled using random effects. RESULTS: 15 RCTs (n = 3431 patients, median treatment 3 and follow-up 15 months) were included. All but 2 used colchicine 1 mg/day. In 5 trials, n = 1301) at risk for cardiovascular disease (coronary artery disease, acute coronary syndrome or stroke, post-angioplasty [2 RCTs], or congestive heart failure), colchicine reduced composite cardiovascular outcomes by ~60 % (risk ratio [RR] 0.44, 95 % confidence interval [CI] 0.28-0.69, p = 0.0004; I(2) = 0 %) and showed a trend towards lower all-cause mortality (RR 0.50, 95 % CI 0.23-1.08, p = 0.08; I(2) = 0 %). In pericarditis or post-cardiotomy, colchicine decreased recurrent pericarditis or post-pericardiotomy syndrome (RR 0.50, 95 % CI 0.41-0.60, p < 0.0001; I(2) = 0 %; 8 RCTs, n = 1635), and post-pericardiotomy or ablation induced atrial fibrillation (RR 0.65, 95 % CI 0.51-0.82, p = 0.0003; I(2) = 31 %; 4 RCTs, n = 1118). The most common adverse event was diarrhea. Treatment discontinuation overall and due to adverse events (RR 4.34, 95 % CI 1.70-11.07, p = 0.002; I(2) = 29 %; 7 RCTs, 83/790 [10.5 %] vs. 11/697 [1.6 %]) was higher in colchicine-assigned patients. CONCLUSIONS: Current RCT data suggests that colchicine may reduce the composite rate of cardiovascular adverse outcomes in a range of patients with established cardiovascular disease. Furthermore, colchicine reduces rates of recurrent pericarditis, post-pericardiotomy syndrome, and peri-procedural atrial fibrillation following cardiac surgery. Further RCTs evaluating the potential of colchicine for secondary prevention of cardiovascular events would be of interest.

BRCA1 shields vascular smooth muscle cells from oxidative stress.

BACKGROUND: Excessive production of reactive oxygen species (ROS), in part via upregulation of DNA damage pathways, is a central mechanism governing pathologic activation of vascular smooth muscle cells (VSMCs). We hypothesized that the breast cancer 1, early onset (BRCA1) gene that is involved in cellular resistance to DNA damage limits ROS production and oxidative stress in VSMCs. METHODS: We evaluated basal and H2O2-stimulated expression of BRCA1 in human aortic smooth muscle cells (HASMCs). In vitro gain-of-function experiments were performed in BRCA1 adenovirus (Ad-BRCA1)-transfected HASMCs. ROS production and expression of Nox1 and its key regulatory subunit p47phox, key components of the ROS-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, were evaluated. In vivo gain-of-function experiments were performed in spontaneously hypertensive (SHR) rats treated with Ad-BRCA1 (5 × 10(10) IU/rat). Blood pressure, vascular ROS generation, Nox1, and p47phox expression were measured. RESULTS: BRCA1 was constitutively expressed in murine, rat, and human smooth muscle cells (SMCs). H2O2 significantly reduced BRCA1 expression with a resultant increase in ROS generation. BRCA1-overexpressing HASMCs were protected against H2O2-induced ROS generation, in part, via downregulation of the ROS-producing NADPH oxidase subunits Nox1 and p47phox. Ad-BRCA1 treatment in SHR rats was associated with a sustained increase in aortic BRCA1 expression, lower aortic ROS production, reduced γH2A.X levels, greater RAD51 foci, and decreases in blood pressure. CONCLUSIONS: BRCA1 is a novel and previously unrecognized target that may shield VSMCs from oxidative stress by inhibiting NADPH Nox1-dependent ROS production. Gene- and/or cell-based approaches that improve BRCA1 bioavailability may represent a new approach in the treatment of diverse vascular diseases associated with an aberrant VSMC phenotype.

Knowledge, attitudes, and practice patterns in surgical management of bicuspid aortopathy: a survey of 100 cardiac surgeons.

OBJECTIVE: Clinical practice guidelines have been established for surgical management of the aorta in bicuspid aortic valve disease. We hypothesized that surgeons' knowledge of and attitudes toward bicuspid aortic valve aortopathy influence their surgical approaches. METHODS: We surveyed cardiac surgeons to probe the knowledge of, attitudes toward, and surgical management of bicuspid aortopathy. A total of 100 Canadian adult cardiac surgeons participated. RESULTS: Fifty-two percent of surgeons believed that the mechanism underlying aortic dilation in those with bicuspid aortic valve was due to an inherent genetic abnormality of the aorta, whereas only 2% believed that altered valve-related processes were involved in this process. Only a minority (15%) believed that bicuspid valve leaflet fusion type is associated with a unique pattern of aortic dilatation aortic phenotype. Sixty-five percent of surgeons recommended echocardiographic screening of first-degree relatives of patients with bicuspid aortic valve. Most surgeons (61%) elected to replace the aorta when the diameter is 45 mm or greater at the time of valve surgery. Fifty-five percent of surgeons surveyed suggested that in the absence of concomitant valvular disease, they would recommend ascending aortic replacement at a threshold of 50 mm or greater. Approximately one third of surgeons suggested that they would elect to replace a mildly dilated ascending aorta (40 mm) at the time of valve surgery. The most common surgical approach (61%) for combined valve and aortic surgery was aortic valve replacement and supracoronary replacement of the ascending aorta, and only a minority suggested the use of deep hypothermic circulatory arrest and open distal anastomosis. More aggressive approaches were favored with greater surgeon experience, and when circulatory arrest was chosen, the majority (68%) suggested they would use antegrade cerebral perfusion. In the setting of aortic insufficiency and a dilated aorta, 42% of surgeons suggested that they would perform valve-sparing surgery. Of note, 40% of respondents used an index measure of aortic size to body surface area in addition to absolute aortic diameter in assessing the threshold for intervention. CONCLUSIONS: This large survey uncovered significant gaps in the knowledge and attitudes of surgeons toward the diagnosis and management of bicuspid aortopathy, many of which were at odds with current guideline recommendations. Efforts to promote knowledge translation in this area are strongly encouraged.

Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials.

BACKGROUND: The choice between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) for revascularisation in patients with diabetes and multivessel coronary artery disease, who account for 25% of revascularisation procedures, is much debated. We aimed to assess whether all-cause mortality differed between patients with diabetes who had CABG or PCI by doing a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing CABG with PCI in the modern stent era. METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from Jan 1, 1980, to March 12, 2013, for studies reported in English. Eligible studies were those in which investigators enrolled adult patients with diabetes and multivessel coronary artery disease, randomised them to CABG (with arterial conduits in at least 80% of participants) or PCI (with stents in at least 80% of participants), and reported outcomes separately in patients with diabetes, with a minimum of 12 months of follow-up. We used random-effects models to calculate risk ratios (RR) and 95% CIs for pooled data. We assessed heterogeneity using I(2). The primary outcome was all-cause mortality in patients with diabetes who had CABG compared with those who had PCI at 5-year (or longest) follow-up. FINDINGS: The initial search strategy identified 3414 citations, of which eight trials were eligible. These eight trials included 7468 participants, of whom 3612 had diabetes. Four of the RCTs used bare metal stents (BMS; ERACI II, ARTS, SoS, MASS II) and four used drug-eluting stents (DES; FREEDOM, SYNTAX, VA CARDS, CARDia). At mean or median 5-year (or longest) follow-up, individuals with diabetes allocated to CABG had lower all-cause mortality than did those allocated to PCI (RR 0.67, 95% CI 0.52-0.86; p=0.002; I(2)=25%; 3131 patients, eight trials). Treatment effects in individuals without diabetes showed no mortality benefit (1.03, 0.77-1.37; p=0.78; I(2)=46%; 3790 patients, five trials; p interaction=0.03). We identified no differences in outcome whether PCI was done with BMS or DES. When present, we identified no clear causes of heterogeneity. INTERPRETATION: In the modern era of stenting and optimum medical therapy, revascularisation of patients with diabetes and multivessel disease by CABG decreases long-term mortality by about a third compared with PCI using either BMS or DES. CABG should be strongly considered for these patients.