Outcomes of Percutaneous Image-Guided and Laparoscopic Cholecystostomies in High-Risk Patients With Acute Calculus Cholecystitis: A Five-Year District General Hospital Experience.

Introduction Acute cholecystitis (AC), inflammation of the gall bladder, is one of the most common emergency surgical presentations. In the UK, approximately 15% of the population is estimated to have gallstones, and approximately 20% of them can develop AC. Laparoscopic cholecystectomy (LC) is considered the definitive management of AC. However, cholecystectomy carries a very high risk of morbidity and mortality in high-risk frail patients with multiple comorbidities who are deemed unfit for surgery. Percutaneous cholecystostomy (PC), both image-guided and laparoscopic, is generally acknowledged as an interim treatment measure before definitive management, which is the LC. Materials and methods This is a retrospective study from the Royal Albert Edward Infirmary, a district general hospital (DGH) based in Wigan, UK. The medical records of all the patients who were admitted to the surgical department and underwent PC between January 2017 and December 2022 were analyzed. Patients with previous hepato-pancreato-biliary (HPB) malignancy, who underwent open cholecystostomy, or those with abdominal ascites were excluded from the study. Information was collected regarding the age, gender, American Society of Anaesthesiologists (ASA) grades, success rates of both procedures as temporary or definitive management, duration of hospital stay, 30-day and 1-year mortality after the procedure, timing of the procedure, and long-term complications after the procedure, particularly those related to cholecystostomy tube dislodgment or blockage. Results Twenty-seven patients who underwent PC were divided into two groups: group A, consisting of 10 patients who underwent laparoscopic cholecystostomies, and group B, consisting of 17 patients who had ultrasound (US)-guided cholecystostomies. The mean age of the patients in group A was 66.7 as compared to 75.1 in group B. Most of the patients were in ASA groups III (14) and IV (10). About 74% of patients had procedures done during the day and 26% had PC at night time. The mean hospital stay was 13.5 days. About 55% of patients had planned elective LC as a definitive management. Following the treatment, two patients died within 30 days, and eight patients passed away within a year. About 40% of the patients had complications related to the tube dislodgment and blockage. Conclusion This study concludes that PC, using both laparoscopic and US-guided techniques, can serve as an interim as well as a definitive measure, particularly in patients who are at high risk for anesthesia and the procedure itself and have multiple comorbidities.

A Good Medical Practice of the Patients' Right to Information: An Audit Cycle of Patient Understanding and Satisfaction With Information Provided to Patients With Acute Pancreatitis.

Introduction Acute pancreatitis (AP), characterized by the inflammation of the pancreas, is a common acute surgical condition accounting for approximately 3% of all surgical admissions with abdominal pain and has an incidence of approximately 56 cases per 100,000 population every year. The General Medical Council (GMC), National Institute for Health and Care Excellence (NICE), and Royal College of Nursing best practice guidelines recommend that such patients and their family members should be provided with both verbal and written information about acute pancreatitis and its management in a way that they can understand. The aim of this audit cycle was to find out the compliance with information provided to patients with acute pancreatitis as per the GMC good medical practice and NICE guidelines and assess their satisfaction. Method A closed-loop audit consisting of two cycles was carried out. Thirty patients who were admitted to the department of general surgery with acute pancreatitis were provided with a questionnaire containing 11 questions asking about the information provided to them about their condition by healthcare professionals; then, interventions were carried out in the form of developing patient information leaflets (PILs) and encouraging healthcare professionals to distribute them and provide information to the patients and their family members. Results Overall, improvements were seen in all aspects of the information being provided to patients, and particularly, more than 100% improvement was seen in patient satisfaction related to the information provided to them in the second cycle after the implementation of interventions. Conclusions This study concludes that patients should be given all the information they require in accordance with their right to information, in line with GMC best practice, NICE, and Royal College of Nursing best practice guidelines. A very effective way to improve the health outcomes and satisfaction of patients is to give them access to a patient information leaflet, which can allow patients to consider their options and understand what can happen during treatment, especially when doctors have limited time to carry out detailed discussions with the patient.

Role of robotic approach in ileal pouch-anal anastomosis (IPAA): A systematic review of the literature.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become standard surgical treatment of choice in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP) in which the medical management fails. Despite the wide use of laparoscopic method, the enhanced and innovative features that come with the robotic platform, such as endo-wrist technology, 3D visualization, surgeon-controlled camera and motion scaling, make it an appealing choice. This study aims to investigate the feasibility and safety of robotic approach for proctectomy or proctocolectomy with IPAA as compared to conventional laparoscopic approach. A systematic review was completed for studies done between 2010 and 2022 comparing the robotic approach with the laparoscopic approach. Nine studies were found to be feasible to be included in this review. In terms of the outcomes, although the mean operating time was slightly higher than the laparoscopic approach, the other outcomes, such as mean blood loss, return of the bowel movement, mean hospital stay, and conversion to open, were found to be significantly lower in the robotic approach as compared to both laparoscopic and conventional open techniques. Despite the overall increased rate of complications combined from all the studies, the rate of significant complications such as anastomotic leaks requiring readmission and return to theater was also found to be substantially less. This study concludes that although robotic approach is in its initial stages for pelvic surgeries, it can be safely employed due to improved dexterity and visibility.

Prevention and Management of Postoperative Ileus: A Review of Current Practice.

Postoperative ileus (POI) has long been a challenging clinical problem for both patients and healthcare physicians alike. Although a standardized definition does not exist, it generally includes symptoms of intolerance to diet, lack of passing stool, abdominal distension, or flatus. Not only does prolonged POI increase patient discomfort and morbidity, but it is possibly the single most important factor that results in prolongation of the length of hospital stay with a significant deleterious effect on healthcare costs in surgical patients. Determining the exact pathogenesis of POI is difficult to achieve; however, it can be conceptually divided into patient-related and operative factors, which can further be broadly classified as neurogenic, inflammatory, hormonal, and pharmacological mechanisms. Different strategies have been introduced aimed at improving the quality of perioperative care by reducing perioperative morbidity and length of stay, which include Enhanced Recovery After Surgery (ERAS) protocols, minimally invasive surgical approaches, and the use of specific pharmaceutical therapies. Recent studies have shown that the ERAS pathway and laparoscopic approach are generally effective in reducing patient morbidity with early return of gut function. Out of many studies on pharmacological agents over the recent years, alvimopan has shown the most promising results. However, due to its potential complications and cost, its clinical use is limited. Therefore, this article aimed to review the pathophysiology of POI and explore recent advances in treatment modalities and prevention of postoperative ileus.

ACTIVATION (PercutAneous Coronary inTervention prIor to transcatheter aortic VAlve implantaTION): A Randomized Clinical Trial.

OBJECTIVES: This study sought to determine if percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) in patients with significant coronary artery disease would produce noninferior clinical results when compared with no PCI (control arm). BACKGROUND: PCI in patients undergoing TAVR is not without risk, and there are no randomized data to inform clinical practice. METHODS: Patients with severe symptomatic aortic stenosis and significant coronary artery disease with Canadian Cardiovascular Society class ≤2 angina were randomly assigned to receive PCI or no PCI prior to TAVR. The primary endpoint was a composite of all-cause death or rehospitalization at 1 year. Noninferiority testing (prespecified margin of 7.5%) was performed in the intention-to-treat population. RESULTS: At 17 centers, 235 patients underwent randomization. At 1 year, the primary composite endpoint occurred in 48 (41.5%) of the PCI arm and 47 (44.0%) of the no-PCI arm. The requirement for noninferiority was not met (difference: -2.5%; 1-sided upper 95% confidence limit: 8.5%; 1-sided noninferiority test P = 0.067). On analysis of the as-treated population, the difference was -3.7% (1-sided upper 95% confidence limit: 7.5%; P = 0.050). Mortality was 16 (13.4%) in the PCI arm and 14 (12.1%) in the no-PCI arm. At 1 year, there was no evidence of a difference in the rates of stroke, myocardial infarction, or acute kidney injury, with higher rates of any bleed in the PCI arm (P = 0.021). CONCLUSIONS: Observed rates of death and rehospitalization at 1 year were similar between PCI and no PCI prior to TAVR; however, the noninferiority margin was not met, and PCI resulted in a higher incidence of bleeding. (Assessing the Effects of Stenting in Significant Coronary Artery Disease Prior to Transcatheter Aortic Valve Implantation; ISRCTN75836930).

Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, a class of compounds that stimulate endogenous erythropoietin production. METHODS: We conducted two randomized, open-label, noninferiority phase 3 trials to evaluate the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD). The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1.25). A key secondary safety end point was the first occurrence of a MACE plus hospitalization for either heart failure or a thromboembolic event. The primary and key secondary efficacy end points were the mean change in hemoglobin from baseline to weeks 24 to 36 and from baseline to weeks 40 to 52, respectively, in each trial (noninferiority margin, -0.75 g per deciliter). RESULTS: A total of 3923 patients were randomly assigned in a 1:1 ratio to receive vadadustat or darbepoetin alfa: 369 in the incident DD-CKD trial and 3554 in the prevalent DD-CKD trial. In the pooled analysis, a first MACE occurred in 355 patients (18.2%) in the vadadustat group and in 377 patients (19.3%) in the darbepoetin alfa group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.11). The mean differences between the groups in the change in hemoglobin concentration were -0.31 g per deciliter (95% CI, -0.53 to -0.10) at weeks 24 to 36 and -0.07 g per deciliter (95% CI, -0.34 to 0.19) at weeks 40 to 52 in the incident DD-CKD trial and -0.17 g per deciliter (95% CI, -0.23 to -0.10) and -0.18 g per deciliter (95% CI, -0.25 to -0.12), respectively, in the prevalent DD-CKD trial. The incidence of serious adverse events in the vadadustat group was 49.7% in the incident DD-CKD trial and 55.0% in the prevalent DD-CKD trial, and the incidences in the darbepoetin alfa group were 56.5% and 58.3%, respectively. CONCLUSIONS: Among patients with anemia and CKD who were undergoing dialysis, vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and correction and maintenance of hemoglobin concentrations. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; INNO2VATE ClinicalTrials.gov numbers, NCT02865850 and NCT02892149.).

Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production. METHODS: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52. RESULTS: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter. CONCLUSIONS: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.).

NHS England-funded CT fractional flow reserve in the era of the ISCHEMIA trial.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) 2016 guidelines (CG95) recommend patients with new stable chest pain be investigated with computed tomography coronary angiography (CTCA). An updated guideline (MTG32) recommended using CT fractional flow reserve (CTFFR) as a gatekeeper to invasive coronary angiography (ICA) for patients with coronary stenosis on CTCA. Subsequently, NHS England negotiated a UK-wide contract with HeartFlow, the provider of CTFFR. We describe our experience with CTFFR and consider the impact of the recent ISCHEMIA trial on these guidelines. METHODS: We prospectively collected ICA and revascularisation data on all patients undergoing CTFFR from January 2019 to March 2020. RESULTS: One-hundred and twenty-five of 140 patients completed CTFFR analysis. Eighty-one patients had CTCA stenosis >50%. Thirty-six had positive CTFFR; 29 underwent ICA with 22 (75.9%) revascularised. Forty-five had negative CTFFR; 14 underwent ICA and four (28.6%) were revascularised. The average cost of investigation per patient (PP) was £971.95. Had these patients undergone ICA directly with no functional test after CTCA, the average cost would be £932.51 PP. CONCLUSION: Our revascularisation rates suggest that CTFFR can potentially be a gatekeeper to ICA but does not necessarily yield cost savings.

Cardiovascular safety and efficacy of vadadustat for the treatment of anemia in non-dialysis-dependent CKD: Design and baseline characteristics.

Current clinical practice guidelines for anemia management in non-dialysis-dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PRO2TECT program comprises 2 global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N = 1751) had hemoglobin <10 g/dL and had not received an ESA within 8 weeks prior to inclusion in the study. Patients recruited into the ESA-treated NDD-CKD trial (N = 1725) had hemoglobin between 8 and 11 g/dL (US) or 9 and 12 g/dL (non-US) and were actively treated with an ESA for anemia associated with CKD. Trial periods in both trials include (1) correction/conversion (weeks 0-23); (2) maintenance (weeks 24-52); (3) long-term treatment (week 53 to end of treatment); and (4) safety follow-up (end-of-treatment to 4 weeks later). The primary safety endpoint is time to first adjudicated major adverse cardiovascular event, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke, pooled across both trials. The primary efficacy endpoint in each trial is change in hemoglobin from baseline to primary evaluation period (weeks 24-36), comparing vadadustat vs darbepoetin alfa treatment groups. Demographics and baseline characteristics are similar among patients in both trials and broadly representative of the NDD-CKD population. These trials will help to evaluate the safety and efficacy of vadadustat for management of anemia associated with NDD-CKD.

Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are currently the mainstay of treatment for anaemia of chronic kidney disease (CKD). Vadadustat is an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that stimulates endogenous erythropoietin formation. The INNO2VATE programme comprises two studies designed to evaluate the safety and efficacy of vadadustat versus the ESA darbepoetin alfa in ameliorating anaemia in patients with dialysis-dependent CKD (DD-CKD). Here we describe the trial design along with patient demographics and baseline characteristics. METHODS: Two Phase 3, open-label, sponsor-blind, active-controlled trials enrolled adults with anaemia of CKD who recently initiated dialysis and had limited ESA exposure (incident DD-CKD trial) or were receiving maintenance dialysis with ESA treatment (prevalent DD-CKD trial). Study periods include correction/conversion (Weeks 0-23), maintenance (Weeks 24-52), long-term treatment (Weeks 53 to end of treatment) and safety follow-up. The primary safety endpoint is the time to the first major adverse cardiovascular event and the primary efficacy endpoint is the change in haemoglobin (baseline to Weeks 24-36). RESULTS: A total of 369 and 3554 patients were randomized in the incident DD-CKD and prevalent DD-CKD trials, respectively. Demographics and baseline characteristics were similar among patients in both trials and comparable to those typically observed in DD-CKD. CONCLUSIONS: The two INNO2VATE trials will provide important information on the safety and efficacy of a novel approach for anaemia management in a diverse DD-CKD population. Demographics and baseline characteristics of enrolled patients suggest that study results will be representative for a large proportion of the DD-CKD population.

Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for treatment of anemia of chronic kidney disease: two randomized Phase 2 trials in Japanese patients.

BACKGROUND: Vadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor in development in Japan for the treatment of chronic kidney disease (CKD)-induced anemia. METHODS: Two Phase 2, multicenter, double-blind, placebo-controlled studies randomized Japanese patients with nondialysis-dependent (NDD, n = 51) or dialysis-dependent (DD, n = 60) CKD-induced anemia to once-daily vadadustat (150, 300 or 600 mg) or placebo. A 6-week, fixed-dose primary efficacy period was followed by a 10-week vadadustat dose adjustment/maintenance period. The primary endpoint was the mean change in hemoglobin (Hb) level from pretreatment to Week 6. RESULTS: Statistically significant (P < 0.01) dose-dependent increases in mean Hb values were observed at Week 6 in all vadadustat groups versus placebo [placebo and vadadustat 150, 300 and 600 mg: -0.47, 0.43, 1.13 and 1.62 (NDD-CKD) and -1.48, -0.28, 0.08 and 0.41 (DD-CKD), respectively]. By Week 16, 91% (NDD-CKD) and 71% (DD-CKD) of vadadustat-treated participants achieved target Hb levels (10.0-12.0 g/dL) and significant dose-dependent changes in iron utilization and mobilization biomarkers were observed with vadadustat. During the primary efficacy period, the incidence of treatment-emergent adverse events (AEs) with placebo and vadadustat 150, 300 and 600 mg was 36, 33, 58 and 54% (NDD-CKD) and 40, 53, 73 and 40% (DD-CKD), respectively. The most common AEs during the primary efficacy period were nausea and hypertension (NDD-CKD) and diarrhea, nasopharyngitis and shunt stenosis (DD-CKD). Of 23 serious AEs in 18 patients, 1 was deemed related (hepatic function abnormal); no deaths were reported. CONCLUSIONS: The efficacy and safety results from these studies support the development of vadadustat for the treatment of anemia in patients with CKD.

Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.

Background: Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease. Methods: In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW). The primary endpoint was mean hemoglobin (Hb) change from pre-baseline average to midtrial (Weeks 7-8) and end-of-trial (Weeks 15-16) and was analyzed using available data (no imputation). Results: Overall, 80, 73 and 68% of subjects in the 300 mg QD, 450 mg QD, and 450 mg TIW dose cohorts respectively, completed the study. For all dose cohorts no statistically significant mean change in Hb from pre-baseline average was observed, and mean Hb concentrations-analyzed using available data-remained stable at mid- and end-of-trial. There was one subject with an Hb excursion >13 g/dL. Overall, 83% of subjects experienced an adverse event (AE); the proportion of subjects who experienced at least one AE was similar among the three dose cohorts. The most frequently reported AEs were nausea (11.7%), diarrhea (10.6%) and vomiting (9.6%). No deaths occurred during the study. No serious AEs were attributed to vadadustat. Conclusions: Vadadustat maintained mean Hb concentrations in subjects on hemodialysis previously receiving epoetin. These data support further investigation of vadadustat to assess its long-term safety and efficacy in subjects on hemodialysis.

An overview of candesartan in clinical practice.

Hypertension is a major risk factor for coronary heart disease, stroke, heart failure and renal disease. The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure 7 defined hypertension as a blood pressure of more than 140/90 mmHg and recommended to initiate treatment with a two-drug combination for stage 2 hypertension (blood pressure of 160-179/100-109 mmHg). The need for drug combinations is clear from a patient and physician perspective as they provide more effective blood pressure lowering, reduce pill burden, improve compliance and decrease hypertension-related morbidity and mortality. Angiotensin II receptor blocker therapy has been proven to be well tolerated and effective in the management of hypertension, chronic heart failure with left ventricular dysfunction and the prevention and progression of diabetic renal disease. Blockers of the renin-angiotensin system are an important component of antihypertensive combination therapy. Thiazide-type diuretics are usually added to increase the blood pressure lowering efficacy. Fixed drug-drug combinations of both principles, such as candesartan/hydrochlorothiazide, are highly effective in lowering blood pressure while providing improved compliance, a good tolerability and largely neutral metabolic profile. In this article, we review the literature for the role of candesartan-based therapy for hypertension, stroke, diabetes mellitus and heart failure.

Right atrial mass in patient undergoing chemotherapy.

A 58-year-old lady, with a Hickman line in situ for chemotherapy for invasive ductal breast carcinoma, presented with fever. Blood cultures grew coagulase negative staphylococci. Transoesophageal echocardiography revealed a mass in the right atrium in the region of the Eustachian apparatus. The Hickman line was removed and the patient was treated for right-sided endocarditis. However, the mass persisted after prolonged intravenous antibiotics and a decision was made to remove it surgically. Histology revealed organised thrombus. The differential investigation of a right atrial mass in this position is discussed.

Perforation of right ventricular free wall by pacemaker lead detected by multidetector computed tomography.

Pacemaker lead perforation is a recognized complication of lead implantation, particularly with active fixation leads. Multidetector computed tomography (MDCT) is emerging as the imaging modality of choice in diagnosing lead perforation, identifying associated sequelae such as pericardial effusion and planning extraction. We present a case illustrating the use of MDCT in a case of right ventricular (RV) lead perforation manifesting 5 days after cardiac resynchronization therapy pacing.