Postoperative outcome of early appendectomy in patients having appendicular mass by laparoscopic surgery

Objective: To determine the frequency of postoperative outcome of early appendectomy in patients having appendicular mass by laparoscopic surgery.Methodology: It was a descriptive & case series study. Study was conducted in the department of surgery Liaquat University Hospital Jamshoro/Hyderabad, during the time period of Jan 2015 to Dec 2017. Patients were both gender and patients aged between 10-40 years having tender and palpable right iliac fossa mass on clinical examination confirmed on ultrasound abdomen as appendicular mass. Patients with mass in right iliac fossa but with associated features like fixed and immobile mass for more than 1 month, bleeding per rectum, history of weight loss, cardio respiratory diseases like recent myocardial infarction, congestive cardiac failure, chronic obstructive pulmonary disease and renal diseases like glomerulonephritis, nephrotic syndrome and renal failure etc, gynecological and obstetrical diseases in female patients were excluded from the study. The postoperative hospital stay was counted and wound infection was noted.Results: During the study period of one year, total of 73 patients with appendicular mass were included in this study.  The age range 10 to 40 years with mean age ± SD (range) was 25.75±9.2 years. Out of them 46 (63.0%) were male whereas 27(37.0 %) were females During operation we found appendicular abscess in 12(16.43%) cases followed by perforated appendix in   10(13.69%) cases, while during operations we found in adhesions in 15(20.5%) cases and difficulty in localisation of appendix 06 (8.21%) cases. The mean hospital stay + SD (range) was 4.91 +1.65 (3-9 days).  Wound infection was seen in 15(20.5 %) cases.Conclusion: Early appendectomy can be safely performed in appendix mass without any increased risk of mortality and morbidity. The outcome of early surgical management of appendicular lump showed benefits for single hospitalization, shorter hospital stay and lower treatment costs

PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT): A prospective longitudinal study protocol investigating the prevalence, severity and determinants of atherosclerotic cardiovascular disease in the young adult Pakistani population

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity, mortality and health expenditures worldwide. Despite having higher ASCVD in the Pakistani population, data on subclinical coronary atherosclerosis in young Pakistanis remain scarce. The PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT) aims to assess the prevalence, severity and determinants of subclinical coronary atherosclerosis among Pakistani men (35-60 years) and women (35-65 years) free of clinically symptomatic ASCVD and will assess 5-year rates of ASCVD events.Methods and analysis: PAK-SEHAT is an ongoing prospective cohort study with 2000 participants from all provinces of Pakistan who will be interviewed at the baseline along with phlebotomy, measurement of carotid intima-media thickness (CIMT) and coronary CT angiography (CCTA). Phlebotomy will be repeated at 2.5 years, whereas CIMT and CCTA will be repeated at 5 years. We will report the frequency of maximal coronary stenosis ≥50% and ≥70%, number of coronary vessels with plaque and the number of coronary segments affected per participant on CCTA. We will use Cox proportional hazards regression models to evaluate the association between baseline characteristics and incident ASCVD events during follow-up. These associations will be presented as HRs with 95% CIs.Ethics and dissemination: The study protocol was approved by the Tabba Heart Institute Institutional Review Board (THI/IRB/FQ/22-09-2021/016). All study procedures are consistent with the principles of the Declaration of Helsinki. Findings of the study will be disseminated via peer-reviewed publications and conference presentations.Trial registration number: NCT05156736

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Outcomes and complications of percutaneous device closure in adults with secundum atrial septal defect

Objectives: To assess immediate outcome and complications of Amplatzer septal occluder percutaneous device for closure of secundum atrial septal defect in adults, and to determine regression in right ventricular size, reduced pulmonary arterial systolic pressure and incidence of device embolization at follow-up. Methods: The single-cohort, ambi-directional, observational study was conducted at the Tabba Heart Institute, Karachi, from January 2013 to July 2018, and comprised patients admitted consecutively for percutaneous atrial septal defect closure. Pre-closure trans-oesophageal echocardiogram was performed in all cases to ensure adequacy of defect margins necessary for device stability. Immediate procedure success and complications were determined by trans-oesophageal echocardiogram, while transthoracic echo was done on follow-up. Data was analysed using SPSS 21. Results: Of the 64 patients, 41(71.9%) were females. The overall mean age was 36.6±14 years. Median size of atrial septal defect was 21mm (interquartile range: 17-26mm). Immediate success was observed in 59(92.2%) patients, and there were 5(8%) acute device embolization events. Small residual atrial septal defect was found in 4(6.3%) cases. On 20-month follow-up, 54(84.4%) patients showed improved symptoms. Repeat transthoracic echo was performed in 39(60.1%) cases, and there were no late embolic events or residual atrial septal defect. Right ventricular size normalized in 34(89.5%) cases, mean pulmonary arterial systolic pressure reduced significantly compared to pre-closure measurement (p<0.001). Conclusion: Percutaneous atrial septal defect closure was found to be safe and effective in adults with secundum atrial septal defect. Timely closure resulted in improved symptoms, right ventricular remodelling and reduced pulmonary arterial systolic Continuous..

PRESENTATION, MANAGEMENT, AND EARLY OUTCOMES OF YOUNG ACUTE CORONARY SYNDROME PATIENTS- ANALYSIS OF 23,560 SOUTH ASIAN PATIENTS FROM 2012-2021

Therapeutic Area: ASCVD/CVD Risk Factors Background: There is a scarcity of literature exploring early outcomes of young acute-coronary-syndrome patients, predominantly in South Asians, who are considered to be at most risk of developing premature coronary artery disease. Therefore, we compared presentation, management, and early outcomes of young vs. old ACS patients and explored predictors of in-hospital mortality. Methods: We extracted data of 23,560 ACS patients presented at Tabba Heart Institute, Karachi, Pakistan, from July 2012-June 2020, from the Chest pain-MI Registry™. Young patients: ≤45 years. Chi-sq/Fischer exact tests assessed the difference between variables in younger vs. older patients. Logistic regression was used to determine predictors of early mortality, and odds ratios along with 95% confidence intervals were reported. Results: The mean age was 59.0±11.4 years, women: 23.5%, and younger patients: 12.3%. Dyslipidemia (34.5% vs. 22.4%), diabetes (52.1% vs. 27.4%) and hypertension (68.3% vs. 42.9%) were higher in older adults. In contrast, Family history of premature coronary artery disease (32.7% vs. 18.1%) and smokeless-tobacco (8.4% vs. 6.5%) was higher in young adults. Younger adults were more likely to present with STEMI (45% vs. 33.2%) and be asymptomatic on presentation (40.8% vs. 36.1%). Median symptom-to-door-time was higher in younger patients (760(192, 3140) vs. 635(186,2735) minutes). Coronary angiography and CABG were higher in older patients; however, PCI was higher in young adults. The use of all medications in first 24 hours except IV anticoagulant and angiotensin receptor blockers was higher in younger adults. In-hospital mortality (4.3% vs. 1.7%) and complications including cardiac arrest (1.9% vs. 0.7%), cardiogenic shock (1.9% vs. 0.9%) and heart failure (1% vs. 0.6%) were more common in older patients. After adjusting for risk factors, older age (2.4, 1.5-3.7) was a significant predictor of early mortality. Other predictors included: STEMI (OR:3.2, 95% CI:1.9-5.5), women (1.4, 1,1-1.8), Killip III/IV (3, 2.4-3.8), cardiac arrest (3.2, 2.2-4.5) and heart failure (1.8, 1.4-2.3) at presentation, Left ventricular ejection fraction (0.9, 0.93-0.95) and PCI (1.3, 1.1-1.7) and CABG (3, 2.3-3.9) at index hospitalization. Conclusion: Younger patients presented differently from their older counterparts as they were likely to be asymptomatic and have STEMI. They had favorable clinical outcomes, which might be explained by the aggressive treatment

Predictors of non-obstructive coronary artery disease in patients undergoing elective coronary angiography

Background: Appropriate patient selection for coronary angiography (CAG) is essential to minimize the unnecessary risk of morbidities and exposure to radiation and iodinated contrast. This becomes even more relevant in low-to-middle-income settings where most health expenditures are out-of-pocket due to lack of medical insurance. We determined predictors of non-obstructive coronaries (NOC) in patients undergoing elective CAG. Methods: CathPCI Registry®, single-center data was extracted for 25,472 patients who had CAG over an eight year period. After excluding patients for compelling conditions or known CAD, 2,984 (11.7%) patients were included in this study. Non-Obstructive Coronaries was defined as \u3c50% left main coronary artery and major epicardial vessel stenosis. Multiple Cox proportional algorithm was employed to report prevalence ratios (PR) of predictors of NOC along with 95% confidence interval. Results: Mean age of patients was 57.9 ± 9.7 years, 23.5% were women. Preprocedural non-invasive testing (NIT) was performed in 46% of the patients; of which 95.5% reported to be positive but only 67.3% were stratified as high risk. Of 2,984 patients undergoing elective CAG, 711 (24%) had NOC. Predictors of NOC included younger age \u3c50 years (PR: 1.3, CI: 1.0-1.5), Women (1.8, 1.5-2.1), low (1.9, 1.5-2.5) and intermediate risk stratification (1.3, 1.0-1.6) on Modified Framingham Risk Score and inappropriate (2.7, 1.6-4.3) and uncertain (1.3, 1.1-1.6) classification of CAG on Appropriate Use Criteria. Patients with heart failure as an indication of CAG (1.7, 1.4-2.0) and No NIT or positive low risk NIT (1.8, 1.5-2.2) were more likely to have NOC. Conclusion: Approximately one out of four patients undergoing elective CAG had NOC. Yield of diagnostic catheterization can be improved by adjudicating NIT especially in younger patients, women, patients with heart failure as an indication of CAG, patients classified as inappropriate on Appropriate Use Criteria and patients categorized as low or intermediate risk on MFR

Characterization of in-house synthesized GNPs and PS conjugation onto their surface.

<p><b>(A)</b> Characterization of in-house synthesized gold nanoparticles. (a) Ultraviolet-visible- near infrared spectra of gold nanoparticles synthesized by exposing various amounts of <i>Aloe vera</i> extract to a fixed volume of HAuCl4 solution (10⁻³ M), keeping the final volume of reaction mixture 10 ml that was made up for each sample by increment in <i>Aloe vera</i> extract content for 24 h. Absorbance is seen to be increasing exhibiting two major peaks, a larger one at 540 nm, the characteristic peak of GNPs. (b) Representative TEM image of gold nanoparticles synthesized using <i>Aloe vera</i> leaf extract exhibiting a large population of spherical gold nanoparticles of approx. 10 nm size. (c) Nanophox particle analysis of synthesized gold nanoparticles. <b>(B)</b> Ultraviolet-visible absorption spectra of gold nanoparticle-photosensitizer conjugate normalized to the maximum absorbance intensity. GNP has signature spectra at 540 nm due to surface plasmon resonance. MB shows absorption peaks at 662 nm and 613 nm. Conjugation of MB to GNP led to appearance of a small peak at 540 nm, intrinsic feature of GNP, which was absent in pure MB spectrum (a). TB spectrum enumerates peaks at 625 nm and 585 nm. GNP-TB conjugate is observed to exhibit an additional shoulder at 540 nm indicating conjugation of GNP to TB (b). Spectrum obtained for the mixture of GNP-MB and GNP-TB (c).</p