Potential application of artificial intelligence in cancer therapy.

PURPOSE OF REVIEW: This review underscores the critical role and challenges associated with the widespread adoption of artificial intelligence in cancer care to enhance disease management, streamline clinical processes, optimize data retrieval of health information, and generate and synthesize evidence. RECENT FINDINGS: Advancements in artificial intelligence models and the development of digital biomarkers and diagnostics are applicable across the cancer continuum from early detection to survivorship care. Additionally, generative artificial intelligence has promised to streamline clinical documentation and patient communications, generate structured data for clinical trial matching, automate cancer registries, and facilitate advanced clinical decision support. Widespread adoption of artificial intelligence has been slow because of concerns about data diversity and data shift, model reliability and algorithm bias, legal oversight, and high information technology and infrastructure costs. SUMMARY: Artificial intelligence models have significant potential to transform cancer care. Efforts are underway to deploy artificial intelligence models in the cancer practice, evaluate their clinical impact, and enhance their fairness and explainability. Standardized guidelines for the ethical integration of artificial intelligence models in cancer care pathways and clinical operations are needed. Clear governance and oversight will be necessary to gain trust in artificial intelligence-assisted cancer care by clinicians, scientists, and patients.

Comparative Efficacy and Safety of Different Stent Types for Pancreatic Fluid Collections: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND AIMS: Drainage of pancreatic fluid collections (PFCs) is required in select cases including infected or symptomatic collections. In this network meta-analysis, we have compared lumen-apposing metal stents (LAMS), fully covered self-expandable metal stents (FCSEMS), and double-pigtail stents (DPS) to identify the most useful stent type in the management of PFCs. METHODS: We reviewed several databases to identify studies that compared DPS or FCSEMS with LAMS and the ones which compared DPS with FCSEMS for the treatment of PFCs. Our outcomes of interest were clinical success, adverse events, technical success, recurrence of PFCs, and procedure duration. Random effects model and frequentist approach were used for statistical analysis. RESULTS: We included 28 studies with 2974 patients. Rate of clinical success was significantly lower with DPS compared to LAMS, OR (95% CI): 0.43 (0.32, 0.59). Rate of recurrence was higher with DPS compared to LAMS, OR (95% CI): 2.06 (1.19, 3.57). We found no significant difference in rate of adverse events between groups. Rate of technical success was higher for FCSEMS compared to LAMS. Procedure duration was significantly shorter for LAMS compared to DPS and FCSEMS. Based on frequentist approach, LAMS was found to be superior to DPS and FCSEMS in achieving higher clinical success, lower rate of adverse events and recurrence, and shorter procedure time. CONCLUSIONS: This network meta-analysis demonstrates the superiority of LAMS over DPS and FCSEMS in the management of PFCs in achieving a higher clinical success, shorter procedure time, and lower rate of recurrence. Some of the analyses are not adequately powered to make firm conclusions, and future large multicenter RCTs are required to further evaluate this issue.

Trust-Based Optimized Reporting for Detection and Prevention of Black Hole Attacks in Low-Power and Lossy Green IoT Networks.

The Internet of Things (IoT) is empowering various sectors and aspects of daily life. Green IoT systems typically involve Low-Power and Lossy Networks (LLNs) with resource-constrained nodes. Lightweight routing protocols, such as the Routing Protocol for Low-Power and Lossy Networks (RPL), are increasingly being applied for efficient communication in LLNs. However, RPL is susceptible to various attacks, such as the black hole attack, which compromises network security. The existing black hole attack detection methods in Green IoT rely on static thresholds and unreliable metrics to compute trust scores. This results in increasing false positive rates, especially in resource-constrained IoT environments. To overcome these limitations, we propose a delta-threshold-based trust model called the Optimized Reporting Module (ORM) to mitigate black hole attacks in Green IoT systems. The proposed scheme comprises both direct trust and indirect trust and utilizes a forgetting curve. Direct trust is derived from performance metrics, including honesty, dishonesty, energy, and unselfishness. Indirect trust requires the use of similarity. The forgetting curve provides a mechanism to consider the most significant and recent feedback from direct and indirect trust. To assess the efficacy of the proposed scheme, we compare it with the well-known trust-based attack detection scheme. Simulation results demonstrate that the proposed scheme has a higher detection rate and low false positive alarms compared to the existing scheme, confirming the applicability of the proposed scheme in green IoT systems.

Cold snare versus cold forceps polypectomy for endoscopic resection of diminutive polyps: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The practices for resection of diminutive colon polyps vary among endoscopists, and U.S. Multi-Society Task force guidelines recommend use of cold snare polypectomy (CSP) for this purpose. In this meta-analysis, we compared CSP and cold forceps polypectomy (CFP) for resection of diminutive polyps. METHODS: Several databases were reviewed to identify randomized controlled trials that compared CSP and CFP for resection of diminutive polyps. The study outcomes of interest were complete resection of all diminutive polyps, complete resection of polyps ≤3 mm in size, failure of tissue retrieval, and polypectomy time. For categorical variables, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated; for continuous variables, mean differences (MDs) with 95% CIs were calculated. Data were analyzed by using a random-effects model, and heterogeneity was assessed by using the I2 statistic. RESULTS: We included 9 studies with 1037 patients. Rate of complete resection of all diminutive polyps was significantly higher in the CSP group (OR, 1.68; 95% CI, 1.09-2.58). Subgroup analysis, including jumbo or large-capacity forceps, found no significant difference in complete resection between groups (OR, 1.43; 95% CI, .80-2.56). We found no significant between-groups in the rates of complete resection of polyps ≤3 mm in size (OR, .83; 95% CI, .30-2.31). Rate of failure of tissue retrieval was significantly higher in the CSP group (OR, 10.13; 95% CI, 2.29-44.74). No significant between-group difference was noted in polypectomy time. CONCLUSIONS: CFP using large-capacity or jumbo biopsy forceps is noninferior to CSP for complete resection of diminutive polyps.

Over-the-Scope Clips Versus Standard Endoscopic Treatment for First Line Therapy of Non-variceal Upper Gastrointestinal Bleeding: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Over-The-Scope Clips (OTSC) use have shown promising results for first line treatment of non-variceal upper gastrointestinal bleeding (NVUGIB). We conducted this meta-analysis to compare outcomes in patients treated with OTSC versus standard endoscopic intervention for first line endoscopic treatment of NVUGIB. METHODS: We reviewed several databases from inception to December 9, 2022 to identify studies comparing OTSC and standard treatments as the first line treatment for NVUGIB. The outcomes assessed included re-bleeding, initial hemostasis, need for vascular embolization, mortality, need for repeat endoscopy, 30 day readmission rate, and need for surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random effect model. Heterogeneity was assessed by I2 statistic. RESULTS: We included 11 studies with 1608 patients (494 patients in OTSC group and 1114 patients in control group). OTSC use was associated with significantly lower risk of re-bleeding (RR, 0.58; 95% CI 0.41-0.82). We found no significant difference in rates of initial hemostasis (RR, 1.05; 95% CI 0.99- 1.11), vascular embolization rates (RR, 0.93; 95% CI 0.40- 2.13), need for repeat endoscopy (RR, 0.78; 95% CI 0.40-1.49), 30 day readmission rate (RR, 0.59; 95% CI 0.17-2.01), need for surgery (RR, 0.81; 95% CI 0.29-2.28) and morality (RR, 0.69; 95% CI 0.38-1.23). CONCLUSIONS: OTSC are associated with significantly lower risk of re-bleeding compared to standard endoscopic treatments when used as first line endoscopic therapy for NVUGIB.

Safety and Efficacy of Endoscopic Retrograde Cholangiopancreatography in Nonagenarians: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent advances in modern medicine have translated into increase in life expectancy in the USA and with that, a rise in the demand for invasive procedures in elderly patients. Endoscopic retrograde cholangiopancreatography (ERCP) is the procedure of choice for managing various benign and malignant pancreatobiliary conditions and can be associated with various adverse events. AIM: We performed a systematic review and meta-analysis to evaluate outcomes of ERCP in nonagenarians. METHODS: A comprehensive literature search was performed in Embase, MEDLINE, Web of Science, and Cochrane Review library until July 2020. Our primary outcomes were the rate of technical success and adverse events in nonagenarians. Secondary outcomes were comparison of technical success and adverse events compared with younger patients. RESULTS: The initial search revealed 4933 studies, of which 24 studies with 5521 patients met our inclusion criteria. Pooled technical success rate of ERCP in nonagenarians was 92%, and pooled adverse event rate was 7.8%. There was no significant difference in technical success rate and overall rate of adverse events comparing ERCP outcomes in nonagenarians with a relatively younger population. The risk of post-ERCP bleeding was significantly higher in nonagenarians compared to younger patients with OR = 1.986 [1.113-3.544], I2 = 0. ERCP-related mortality was also significantly higher in nonagenarians compared to younger patients with OR = 4.720 [1.368-16.289], I2 = 0. CONCLUSION: There was no significant difference in technical success rate and risk of adverse events related to ERCP in nonagenarians compared to younger patients. However, the risk of bleeding and procedure-related mortality was significantly higher.

Outcomes of Endoscopic Submucosal Dissection for Treatment of Superficial Pharyngeal Cancers: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Studies evaluating the role of endoscopic submucosal dissection (ESD) in the management of superficial pharyngeal cancers have reported promising results. This meta-analysis evaluates the efficacy and safety of ESD in the management of superficial pharyngeal cancers. METHODS: We reviewed several databases from inception to September 03, 2020, to identify studies evaluating the efficacy and safety of ESD in the management of superficial pharyngeal cancers. Our outcomes of interest were en bloc resection rate, complete resection rate, adverse events, and rates of local recurrence. Pooled rates with 95% confidence intervals (CI) for all outcomes were calculated using random-effect model. Heterogeneity was assessed by I2 statistic. We assessed publication bias by using funnel plots and Egger's test. We conducted meta-regression analysis to explore heterogeneity in analyses. RESULTS: Ten studies were included in analyses. All studies were from Asia. Pooled rates (95% CI) for en bloc resection and complete resection were 94% (87%, 97%) and 72% (62%, 80%), respectively. The pooled rates (95% CI) for adverse events and local recurrence were 10% (5%, 17%) and 1.9% (0.9%, 4%), respectively. Most of the analyses were limited by substantial heterogeneity. On meta-regression analysis, the heterogeneity was explained by size of tumor and histology. Funnel plots and Egger's test showed no evidence of publication bias. CONCLUSIONS: This meta-analysis including studies from Asian countries demonstrated that ESD is an efficacious and safe option in the management of superficial pharyngeal cancers. More studies and studies from Western countries are needed to further validate these findings.

Efficacy and Safety of N-Butyl 2 Cyanoacrylate Injection for Treatment of Gastric Varices: A five year experience from a tertiary care hospital in Karachi, Pakistan.

Objectives: To evaluate the efficacy and safety of N-Butyl 2 Cyanoacrylate injection for treatment of gastric varices. Methods: This was a retrospective observational cohort conducted at Medical Unit IV, Department of Gastroenterology, JPMC, Karachi from January 2014 to December 2018 (five years). All patients irrespective of age and gender that presented to the emergency department with complain of hematemesis or stigmata of UGIB were potential candidates. Once they were resuscitated and endoscopic evidence of gastric varices requiring intervention was found, the patients were inducted into the study. N-Butyl 2 Cyanoacrylate injection was performed until hemostasis and obliteration of gastric varices was achieved. Response to therapy was analyzed at three weeks with repeat endoscopy. Mortality was analyzed at six weeks. Major and minor complications recorded as well. Results: A total of 159 patients were inducted into the study. Isolated gastric varices Type-I was mostly encountered. A singular session was sufficient to achieve obliteration and hemostasis in over three quarter of the patients. Complications affected 11.30% of the patients. Six weeks mortality was exceptionally low at 1.20%. Conclusions: N-Butyl 2 Cyanoacrylate is safe and effective for treatment of gastric varices. There were few complications seen with this procedure in this study. It significantly reduces mortality at six weeks.

Sequencing of novel agents in relapsed/refractory B-cell acute lymphoblastic leukemia: Blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia.

BACKGROUND: The availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity. METHODS: In this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared. RESULTS: Among 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety-two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09). CONCLUSIONS: Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.

Colloidal quantum dots lasing and coupling in 2D holographic photonic quasicrystals.

Global research on the solution-processable colloidal quantum dots (CQDs) constitutes outstanding model systems in nanoscience, micro-lasers, and optoelectronic devices due to tunable color, low cost, and wet chemical processing. The two-dimensional (2D) CQDs quasicrystal lasers are more efficient in providing coherent lasing due to radiation feedback, high-quality-factor optical mode, and long-range rotational symmetry. Here, we have fabricated a 2D quasicrystal exhibiting 10-fold rotational symmetry by using a specially design pentagonal prism in the optical setup of a simple and low-cost holographic lithography. We developed a general analytical model based on the cavity coupling effect, which can be used to explain the underlying mechanism responsible for the multi-wavelength lasing in the fabricated 2D CQDs holographic photonic quasicrystal. The multi-wavelength surface-emitting lasers such as λ0 = 629.27 nm, λ1 = 629.85 nm, λ-1 = 629.06 nm, λ2 = 630.17 nm, and λ-2 = 628.76 with a coupling constant κ = 0.38 achieved from the 2D holographic photonic quasicrystal are approximately similar with the developed analytical model based on cavity coupling effect. Moreover, the lasing patterns of the 2D CQDs photonic quasicrystal laser exhibit a symmetrical polarization effect by rotating the axis of polarization with a difference of 1200 angle in a round trip. We expect that our findings will provide a new approach to customize the 2D CQDs holographic photonic quasicrystal lasers in the field of optoelectronic devices and miniature lasing systems.

Comparison of clinical outcomes of multiple plastic stents and covered metal stent in refractory pancreatic ductal strictures in chronic pancreatitis- a systematic review and meta-analysis.

BACKGROUND: Symptomatic pancreatic duct (PD) strictures in chronic pancreatitis refractory to single plastic stenting are usually managed by placement of multiple plastic stents (MPS). Fully covered self-expanding metallic stents (FCSEMS) have also been used in the management of these patients. However, the overall efficacy and safety of different types of stents is unclear from the currently available studies. We performed this meta-analysis to assess the efficacy and complications from MPS and FCSEMS in patients with PD strictures refractory to treatment with single plastic stents. METHODS: Several electronic databases were searched for all the studies evaluating the outcome of placement of multiple plastic stents and fully covered metal stents in patients with PD strictures refractory to single plastic stenting. We calculated the Weighted Pooled Ratio (WPR) with Confidence Interval (CI) between the MPS and FCSEMS. RESULTS: A total of 13 studies (including 2 abstracts) were included in the analysis. MPS were placed in 106 patients and FCSEMS in 192 patients. Improvement in pain after stenting (P = 0.794), risk of recurrence of pain after removal of stent (P = 0.48) and stricture recurrence after stent removal (P = 0.52) were comparable between MPS and FCSEMS. Risk of endoscopic re-intervention was also comparable between metal stents and MPS. However, FCSEMS was associated with overall higher risk of adverse events (P < 0.0001). CONCLUSION: FCSEMS are comparable to multiple plastic stents in the treatment of symptomatic refractory PD strictures. However, use of FCSEMS is associated with increased risk of adverse events.

Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Studies evaluating the role of routine second-look endoscopy in patients with acute upper GI bleed because of peptic ulcer disease (PUD) have reported conflicting results. This meta-analysis evaluates the usefulness of routine second-look endoscopy in these patients. METHODS: We reviewed several databases from inception to September 15, 2020 to identify randomized controlled trials (RCTs) that compared routine second-look endoscopy with no planned second-look endoscopy in patients with acute upper GI bleed because of PUD. Our outcomes of interest were recurrent bleeding, mortality, need for surgery, and mean number of units of blood transfused. For categorical variables, we calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs); for continuous variables, we calculated standardized mean difference with 95% CIs. Data were analyzed using a random effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to ascertain the quality of evidence. RESULTS: We included 9 RTCs comprising 1452 patients; 726 patients underwent planned/routine second-look endoscopy and 726 did not. We found no significant difference in recurrent bleeding (RR, .79; 95% CI, .51-1.23), need for surgery (RR, .58; 95% CI, .29-1.15), mortality (RR, .69; 95% CI, .33-1.45), or mean number of units of blood transfused (standardized mean difference, -.06; 95% CI, -.19 to .07). Quality of evidence ranged from low to moderate based on the GRADE framework. CONCLUSIONS: Single endoscopy with complete endoscopic hemostasis is not inferior to routine second-look endoscopy in reducing the risk of recurrent bleeding, mortality, or need for surgery in patients with acute upper GI bleed because of PUD.

Efficacy and safety of supplemental intravenous lidocaine for sedation in gastrointestinal endoscopic procedures: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Some studies have shown that intravenous (IV) lidocaine reduces the dose requirement of propofol in GI endoscopic procedures. We conducted this study to evaluate the efficacy and safety of the combination of IV lidocaine and propofol compared with propofol alone in GI endoscopic procedures. METHODS: We reviewed several databases from inception to October 13, 2020, to identify randomized controlled trials (RCTs) that compared the role of IV propofol and lidocaine with IV propofol plus placebo for sedation in endoscopic procedures. Our outcomes of interest were the differences in total dose of propofol administered, procedure time, and intraoperative adverse events. For categorical variables, we calculated pooled risk ratios with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effect model. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework to ascertain the quality of evidence. RESULTS: We included 5 randomized controlled trials with 318 patients. We found that the total dose of propofol administered was significantly lower in the lidocaine group than the control group (SMD, -0.76; 95% CI, -1.09 to -0.42). We found no significant difference in procedure time (SMD, 0.16; 95% CI, -0.26 to 0.57) or adverse events (risk ratio, 0.60; 95% CI, 0.35-1.03) between the groups. There was moderate to substantial heterogeneity in the data. Quality of evidence based on the GRADE framework ranged from low to moderate. CONCLUSIONS: Moderate quality of evidence suggests that IV lidocaine decreases the dose of propofol administered for GI endoscopic procedures.

Efficacy of empiric esophageal dilation in patients with non-obstructive dysphagia: systematic review and meta-analysis.

BACKGROUND AND AIMS: Empiric esophageal dilation is frequently performed for non-obstructive dysphagia. Studies evaluating its efficacy have reported conflicting results. In this meta-analysis, we have evaluated the efficacy of esophageal dilation in the management of non-obstructive dysphagia. METHODS: We reviewed several databases from inception to 26 May 2021 to identify randomized controlled trials (RCTs) and observational studies that evaluated the role of empiric esophageal dilation for non-obstructive dysphagia. Our outcomes of interest were clinical success (improvement in dysphagia after dilation) and difference in post-operative dysphagia score between groups. For categorical variables, we calculated pooled odds ratios (OR) with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effects model. We used GRADE framework to ascertain the quality of evidence. RESULTS: We included 4 studies (3 RCTs and one observational) with 243 patients; there were 133 treated with empiric dilation and 110 controls. We found no significant difference in clinical success (OR (95% CI) 1.91 (0.89, 4.08)) or post-procedure dysphagia score between groups (SMD (95% CI) 0.38 (-0.37, 1.14)). Our findings remained consistent on subgroup analysis including RCTs only. Quality of evidence ranged from low to very low based on GRADE framework. CONCLUSIONS: Our meta-analysis does not support the use of empiric esophageal dilation in patients with non-obstructive dysphagia. More studies are required to confirm these findings.

Peroral Endoscopic Myotomy Is a Safe and Feasible Option in Management of Esophageal Diverticula: Systematic Review and Meta-Analysis.

Esophageal diverticula can cause significant symptoms and affect the quality of life. There has been recent interest in the use of peroral endoscopic myotomy in the management of esophageal diverticula (D-POEM). In this meta-analysis, we have evaluated the efficacy and safety of D-POEM in the management of esophageal diverticula. Several databases were reviewed from inception to 6/19/2020 to identify the studies evaluating the feasibility, efficacy and safety of D-POEM in the management of esophageal diverticula. Our outcomes of interest were technical success, adverse events and difference in mean pre- and post-procedure symptom score. We performed subgroup analysis including patients with Zenker's diverticulum who underwent POEM (Z-POEM). Pooled rates with 95% confidence intervals (CI) for all outcomes were calculated using random effect model. We calculated standard mean difference (SMD) with 95% CI to compare mean pre- and post-procedure symptom score. We included 7 studies with 233 patients. For D-POEM, pooled rates (95% CI) for technical success and adverse events were 95% (91%, 97%) and 6% (3%, 10%) respectively. For Z-POEM, pooled rates (95% CI) for technical success and adverse events were 95% (90%, 97%) and 6% (3%, 10%) respectively. Mean post-procedure symptom score for all patients who underwent D-POEM was significantly lower compared to mean pre-procedure symptom score, SMD (95% CI) 2.17 (1.51, 2.83).  This meta-analysis demonstrated that D-POEM is a safe and feasible option for patients with symptomatic esophageal diverticula.

Chlorfenapyr containing anions uptake from industrial wastewater by ethylene glycol functionalized benzyl dimethyl tetradecyl ammonium bromide membrane.

The preservation of water and wastewater treatment has become a global challenge. The concentration of anions such as chlorides, fluorides, cyanides, and perchlorates above the permitted levels in water is harmful to human and aquatic life. Chlorfenapyr is an insecticide that contains the aforesaid anions and is abundantly present in industrial wastewater. This research is focused on the removal of these anions from wastewater by ethylene glycol functionalized benzyl dimethyl tetradecyl ammonium bromide immobilized on soluble polymer anion exchange membrane. The real wastewater samples rich in chlorfenapyr from two different sources (industrial and pond) were analyzed. Membrane efficiency was more than 50 ppm for each anion in a single fold. The double folds of membrane showed enhanced uptake and separation efficiency for chloride, fluoride, and cyanide from wastewater samples between 0.01 and 0.02 ppm down to lethal concenetrations values (LD 50). The membrane shows maximum separation efficiency between the pH ranges of 6-7. The interference effect on membrane separation efficiency showed that the replacement ability of sample anions was in the order of fluoride > chloride > perchlorate > cyanide. This high replacement efficiency of fluoride and chloride is attributed to the more chemical interactions of these anions with membrane.

Effectiveness of Sofosbuvir and Daclatasvir in treatment of Hepatitis-C: An experience of tertiary care hospital in Karachi.

OBJECTIVE: To assess the effectiveness of Sofosbuvir (SOF) and Daclatasvir (DCV) in patients with chronic hepatitis C (CHC), compensated cirrhosis (CC) and decompensated cirrhosis (DCLD) either treatment naïve or experienced. METHODS: This was a prospective, observational study, conducted from January 2017 to December 2018 at Jinnah Postgraduate Medical Centre, Karachi. All patients above 12 years of age with detectable HCV RNA PCR were included. Patients were divided into three groups: CHC, CC and DCLD. SOF and DCV for 12 or 24 weeks were given. Ribavirin (RBV) was given to treatment experienced and cirrhotic patients. Primary outcome was End of Treatment Response (ETR) and secondary outcome was Sustained Virological Response (SVR) at post treatment week 12 or 24. RESULTS: Total 300 patients with mean age of 40.49 ± 13.86 were enrolled. Majority were females 174 (58%). CHC were 200 (66.6%) while cirrhotic were 100 (33.4%). Treatment naïve patients were 267 (89%) and 33 (11%) patients were experienced. Most common genotype was 3 (83%). ETR was achieved in 292 (97.33%) and SVR in 265 (88.33%) patients respectively. CONCLUSION: SOF plus DCV with or without RBV is a highly effective treatment for chronic HCV and is still used in many centers of Pakistan. This regimen has excellent results for GT-3. The outcomes are mainly influenced by the presence or absence of cirrhosis.

No Association Linking Short-Term Proton Pump Inhibitor Use to Dementia: Systematic Review and Meta-analysis of Observational Studies.

INTRODUCTION: Long-term use of proton pump inhibitors (PPIs) has been associated with a wide variety of potentially serious adverse effects including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions. We aimed to evaluate this proposed association further and to assess the quality of the evidence in its support. METHODS: We searched MEDLINE, EMBASE, ISI Web of Science, and Cochrane databases for studies examining a link between PPI use and dementia, up to February 2019. Studies reporting summary results as hazard ratio (HR) or odds ratio (OR) were pooled using the DerSimonian and Laird random-effects model for meta-analyses. Methodological quality of individual observational studies was assessed using the Newcastle-Ottawa scale and the overall quality of evidence rated as per the GRADE approach. RESULTS: We identified and included 11 observational studies comprising 642,949 subjects; 64% were women. Most studies were short-term ranging from 5 to 10 years. There were 158,954 PPI users and 483,995 nonusers. For studies summarizing data as adjusted HR, pooled HR for all causes of dementia was 1.10 (0.88-1.37); for Alzheimer dementia only, it was 1.06 (0.72-1.55). For studies summarizing data as adjusted OR, pooled OR for all causes of dementia was 1.03 (0.84-1.25) and for Alzheimer dementia only 0.96 (0.82-1.11). Per Newcastle-Ottawa scale assessment, 10 studies were of high quality and 1 was of moderate quality. By applying GRADE methodology, quality of evidence for both outcomes was very low. DISCUSSION: We found no evidence to support the proposed association between PPI use and an increased risk of dementia. PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.

Emergent versus urgent ERCP in acute cholangitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Acute cholangitis is characterized by abdominal pain, fever, and jaundice. Most patients respond to medical management with intravenous hydration and antibiotics. About 20% to 30% require biliary drainage, and ERCP is the procedure of choice. We conducted a systematic review and meta-analysis to evaluate the impact of emergent biliary drainage on patient outcomes. METHODS: A comprehensive literature review was conducted by searching the Embase and PubMed databases from inception to April 2019 to identify all studies that evaluated the impact of timing of ERCP on patient outcomes. Our primary outcome was in-hospital mortality (IHM), and secondary outcomes were length of stay (LOS), organ failure, and 30-day mortality. Fixed and random effects models were used to generate pooled measures of IHM, 30-day mortality, and LOS. RESULTS: Nine observational studies involving 7534 patients were included in the primary meta-analysis. IHM was significantly lower in patients who underwent emergent biliary drainage within 48 hours (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.28-0.98). As a sensitivity analysis, we pooled the data from 2 population registry studies of 81,893 patients, which yielded consistent results for the main outcomes. LOS was also significantly lower in patients who underwent ERCP within 48 hours with a mean difference of 5.56 days (95% CI, 1.59-9.53). Patients who underwent emergent ERCP also had lower odds of 30-day mortality (OR, 0.39; 95% CI, 0.14-1.08) and organ failure (OR, 0.69; 95% CI, 0.33-1.46). CONCLUSIONS: Our study reveals that performing emergent ERCP within 48 hours in patients with acute cholangitis is associated with lower IHM, 30-day mortality, organ failure, and shorter LOS.

Efficacy and safety of tranexamic acid in acute upper gastrointestinal bleeding: meta-analysis of randomised controlled trials.

BACKGROUND: Studies evaluating the role of tranexamic acid in acute upper GI bleeding (UGIB) have reported conflicting results. In this systematic review, we have evaluated the efficacy and safety of tranexamic acid in UGIB. METHODS: We searched several databases from inception to June 6, 2020 to identify randomised controlled trials (RCTs) that compared tranexamic acid and placebo in UGIB. Our outcomes of interest were mortality, rebleeding, all thromboembolic events, venous thromboembolic events, need for transfusion, endoscopic intervention and surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using fixed effect model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess the certainty of evidence. RESULTS: We included 12 RCTs comprising 14,100 patients. We found no significant difference in mortality, pooled RR (95% CI) 0.87 (0.74-1.01), rebleeding, pooled RR (95% CI) 0.90 (0.79-1.02), need for surgery, pooled RR (95% CI) 0.86 (0.73-1.02), need for transfusion, pooled RR (95% CI) 1.00 (0.99-1.01) or thromboembolic events, RR (95% CI) 1.16 (0.87-1.56) between treatments. We found an increased risk of venous thromboembolic events with tranexamic acid, pooled RR (95% CI) 1.94 (1.23-3.05). Certainty of evidence based on the GRADE framework for the different outcomes ranged from low to very low. CONCLUSIONS: Tranexamic acid does not improve outcomes in UGIB and may increase the risk of venous thromboembolic events.