A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal.

BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.

Implantable Peripheral Nerve Stimulation for Peripheral Neuropathic Pain: A Systematic Review of Prospective Studies.

Peripheral nerve stimulation (PNS) has been utilized for over 50 years with accumulating evidence of efficacy in a variety of chronic pain conditions. The level and strength of evidence supporting the use of PNS for peripheral neuropathic pain remains unclear. The purpose of this review is to synthesize data from prospective studies on the efficacy of PNS for neuropathic pain as it pertains to pain intensity, neurological deficits/neuropathy (e.g., weakness, sensory deficits, gait/balance), and other secondary outcomes (quality of life, satisfaction, emotional functioning, and adverse events). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, this review identified articles from MEDLINE(R), EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Overall, per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, pooled results demonstrate very low quality or low quality of evidence supporting modest to substantial improvement in pain and neurological function after PNS implantation for treatment of peripheral neuropathic pain. PNS for phantom limb pain was the only indication that had moderate level evidence. Future prospective and well-powered studies are warranted to assess the efficacy of PNS for peripheral neuropathic pain.

Neuromodulation Therapy for Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients who have received chemotherapy. The role of neuromodulation therapy in treating pain and improving neurological function in CIPN remains unclear and warrants evidence appraisal. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review to assess change in pain intensity and neurological function after implementation of any neuromodulation intervention for CIPN. Neuromodulation interventions consisted of dorsal column spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), or peripheral nerve stimulation (PNS). In total, 15 studies utilized SCS (16 participants), 7 studies utilized DRG-S (7 participants), and 1 study utilized PNS (50 participants). Per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria, there was very low-quality GRADE evidence supporting that dorsal column SCS, DRG-S, and PNS are associated with a reduction in pain severity from CIPN. Results on changes in neurological function remained equivocal due to mixed study findings on thermal sensory thresholds and touch sensation or discrimination. Future prospective, well-powered, and comparative studies assessing neuromodulation for CIPN are warranted.

Creating a Single Inflow Orifice From Living Donor Kidney Allografts With Multiple Renal Arteries.

Background: Multiple renal arteries (MRA) are often encountered during living-donor kidney transplantation (LDKT), requiring surgeons to pursue complex renovascular reconstructions prior to graft implantation. With improvements in reconstruction and anastomosis techniques, allografts with MRA can be successfully transplanted with similar outcomes to allografts with a single renal artery. Here, we describe in detail various surgical techniques for reconstruction of MRA grafts with the intent of creating a single arterial inflow. Methods: We retrospectively reviewed the medical records of all LDKT recipients with laparoscopically procured MRA kidneys between March 2008 and July 2021. Recipient and donor characteristics, operative data, type of reconstruction, and recipient outcomes were analyzed. The primary outcomes were the incidence of developing delayed graft function (DGF) and/or a vascular or urological complication within 12 months post-transplant. Results: Seventy-three LDKT recipients of MRA donor allografts were evaluated. Two renal arteries (RA) were encountered in 62 allografts (84.9%) and three RA in 11 allografts (15.1%). Renal artery reconstruction was performed in 95.8% (70/73) of patients. Eighteen different reconstruction techniques of MRA were utilized, the most common being side-to-side anastomosis in allografts with two RA (N = 44) and side-to-side-to-side anastomosis in allografts with three RA (N = 4). Interposition grafting was performed in seven cases (9.6%). A single ostium was created in 69 cases (94.5%), and the median warm ischemia time was 27 (range 20-42) minutes. None of the patients developed DGF or post-operative vascular or urological complications. Median creatinine at 3, 6, and 12 months post-transplant remained stable at 1.1 mg/dl. With a median follow-up of 30.4 months post-transplant, only one graft failure has been observed-death-censored graft survival was 98.6%. Conclusion: Complex reconstruction techniques to create a single renal artery ostium for graft implantation anastomosis in allografts with MRA show acceptable warm ischemic times, with no increased risk of post-operative vascular or urological complications.

Peripheral access size evaluation in transfemoral transcatheter aortic valve replacement.

BACKGROUND/AIM: Peripheral access vessel dimensions in the general patient population screened for transcatheter aortic valve replacement (TAVR) can offer insight into the indications for pre-TAVR computed tomography angiography (CTA) assessment. We seek to determine peripheral access vessel sizes in patients screened for TAVR and association with patient characteristics. MATERIALS AND METHODS: All patients with severe, symptomatic aortic stenosis screened for TAVR at a high-volume center from April 2012 to March 2019 were retrospectively reviewed. For each patient, contrast-enhanced CTA was used to determine the minimal luminal diameters (MLDs) of the transfemoral access vessels, as measured between the inguinal ligament and the deep femoral artery for the femoral artery, and proximal to the inguinal ligament for the external and common iliac arteries, respectively. Paired and independent samples t-tests were used to compare means and regression analyses were performed to determine factors associated with MLD. RESULTS: A total of 1049 screened patients were included of which 826 (78.7%) underwent TAVR and 551 (52.5%) were male. The mean age was 80.6 (±9.6) years and the mean body mass index (BMI) was 26.7 (±5.9) kg/m2 . About 152 (14.5%) had peripheral vascular disease and 153 (14.6%) had chronic kidney disease. The mean (±2 standard deviations) MLDs of the right and left femoral arteries were 7.73 mm (4.68-10.78) and 7.68 mm (4.63-10.72), respectively. Male sex and BMI were associated with larger average femoral MLD while hyperlipidemia, hypertension, smoking, peripheral vascular disease, and coronary artery disease were inversely associated. CONCLUSION: Most patients screened for TAVR have minimum peripheral access vessel sizes exceeding the recommended minimum access route diameters of modern transcatheter heart valves. As sheath sizes decrease, clinicians must carefully judge patient individual risk factors to determine whether a pre-TAVR CTA assessing peripheral access vessel dimensions and anatomical contraindications is indicated. Larger studies and randomized controlled trials are required to compare the outcomes of TAVR with and without preoperative CTA.

Exploring a Novel Fasudil-Phospholipid Complex Formulated as Liposomal Thermosensitive in situ Gel for Glaucoma.

PURPOSE: Fasudil hydrochloride (Fas), a rho-associated protein kinase inhibitor, proved to be promising for glaucoma management owing to its IOP lowering and antioxidant effects. However, its highly hydrophilic nature limits ocular permeation and bioavailability. Hence, the study objective was the development of Fas loaded vesicular system with high entrapment efficiency formulated as a thermosensitive gel for local administration aiming to enhance ocular retention and permeation and hence therapeutic efficacy. METHODS: Fasudil complex with phospholipid (Fas/PL) was prepared by solvent evaporation technique and characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Fas/PL was further formulated as liposomes by methanol injection method and characterized regarding colloidal properties, entrapment efficiency (EE%) and in vitro drug release. The prepared liposomes were incorporated into an optimized thermosensitive in situ gel (Fas/PL-LipoP407/HPMCgel) selected based on gelling time and temperature and rheological properties. The effect of incorporation into gel on the in vitro characteristics of liposomes was investigated. The in vitro mucoadhesive potential, ex vivo permeation, irritability and efficacy in a glaucoma rabbit model were also assessed. RESULTS: FT-IR and XRD suggested interactions between Fas and PL, proposing complexation. Fas/PL liposomal dispersions showed good colloidal properties (particle size: 132.5 ± 1.6 nm, zeta potential: -21.6 ± 0.9 and %EE 78.6 ± 0.3%) with sustained drug release. In situ thermosensitive gel (20% poloxamer 407 and 0.5% HPMC) showed optimum gelling properties. The selected gel formulation reduced burst release of the drug, enhanced mucoadhesive properties and prolonged corneal permeation ex vivo. HET-CAM test confirmed that the prepared formulations were non-irritant. In vivo pharmacodynamic study indicated improved bioavailability and significantly lower intraocular pressure (IOP) of Fas/PL-LipoP407/HPMC gel compared to drug solution and liposomal dispersion. CONCLUSION: The results present Fas/PL-LipoP407/HPMC gel as a potential platform for ophthalmic delivery of fasudil with improved pharmaceutical attributes and enhanced bioavailability and efficacy in glaucoma.

How to Deal With Kidney Retransplantation-Second, Third, Fourth, and Beyond.

Kidney transplantation is the best health option for patients with end-stage kidney disease. Ideally, a kidney transplant would last for the lifetime of each recipient. However, depending on the age of the recipient and details of the kidney transplant, there may be a need for a second, third, fourth, or even more kidney transplants. In this overview, the outcome of multiple kidney transplants for an individual is presented. Key issues include surgical approach and immunologic concerns. Included in the surgical approach is an analysis of transplant nephrectomy, with indications, timing, and immunologic impact. Allograft thrombosis, whether related to donor or recipient factors merits investigation to prevent it from happening again. Other posttransplant events such as rejection, viral illness (polyomavirus hominis type I), recurrent disease (focal segmental glomerulosclerosis), and posttransplant lymphoproliferative disease may lead to the need for retransplantation. The pediatric recipient is especially likely to need a subsequent kidney transplant. Finally, noncompliance/nonadherence can affect both adults and children. Innovative approaches may reduce the need for retransplantation in the future.

Surgical Management of Upper Urinary Tract Urothelial Cell Carcinoma with Venous Tumor Thrombus: A Liver Transplant-Based Approach.

Upper urinary tract urothelial cell carcinoma (UTUC) with venous tumor thrombus (TT) that extends into the renal vein (RV) and inferior vena cava (IVC) is a rare entity and its management is a surgical challenge. We report the largest single experience of surgical management of UTUC and accompanying venous TT with radical nephroureterectomy and tumor thrombectomy (RNATT) using transplant-based (TB) surgical techniques. From September 2003 to June 2021, nine patients with UTUC and venous TT underwent RNATT. Demographics, disease characteristics, surgical details, 30-day postoperative complications, and overall survival (OS) were analyzed. All nine patients had extension of the TT into the RV. Of those, seven had additional extension of the TT into the IVC. Venous TT level was categorized as 0 (n = 2), I (n = 2), II (n = 4), and IIIa (n = 1). Median tumor size was 12 cm (range 3-20 cm). Median estimated blood loss was 300 (range 150-1000) cc. One patient was still alive at last follow-up (4 months), and in total, eight patients have died with a median time-to-death of 12 months (range 10 days-24 months). RNATT using TB maneuvers like liver mobilization and pancreas-spleen en bloc mobilization provide excellent exposure to the retroperitoneal space and enable the safe removal of UTUC with venous TT.

Recurrent Renal Allograft Torsion After Simultaneous Kidney and Pancreas Transplantation: Is it Still Possible to Salvage the Graft? A Case Report.

BACKGROUND: Kidney allograft torsion (KAT) is defined as a rotation of the renal allograft around its vascular pedicle. It is a rare complication with high rate of graft loss. The nonspecific presentation and inability to provide a definitive diagnosis by imaging, mainly in cases of partial torsion, often delay the diagnosis and treatment. We report a case of recurrent complete torsion of the renal allograft after simultaneous kidney and pancreas transplantation, requiring 2 emergency exploratory laparotomies. CASE REPORT: A 38-year-old woman with a history of intraperitoneal simultaneous kidney and pancreas transplantation underwent 2 separate emergency exploratory laparotomies secondary to complete renal allograft torsion, respectively, 7 and 11 months after the transplant. In both episodes, no adhesions were encountered. During the first operation, nephropexy was performed. During the second operation, an abdominal wall mesh was placed and fixed to the abdominal wall. Acute kidney injury related to KAT recovered in both occasions with a creatinine of 1.3 mg/dL at 4 months follow-up. CONCLUSIONS: Renal torsion always should be suspected in intraperitoneally placed kidneys presenting with nonspecific symptoms, abdominal pain, oliguria, and worsening kidney function. Surgical exploration should be considered to salvage the renal graft. This case illustrates the reversibility of a severe injury related to this vascular complication with an adequate return to baseline kidney function even when diagnosis and surgical treatment of KAT might be delayed secondary to its misleading clinical presentation.

Sex differences in outcomes following coronary artery bypass grafting: a meta-analysis.

OBJECTIVES: Previous reports have found females are a higher risk of morbidity and mortality following isolated coronary artery bypass grafting (CABG). Here, we describe the differences in outcomes following isolated CABG between males and females. METHODS: Following a systematic literature search, studies reporting sex-related outcomes following isolated CABG were pooled in a meta-analysis performed using the generic inverse variance method. The primary outcome was operative mortality. Secondary outcomes included rates of stroke, repeat revascularization, myocardial infarction, major adverse cardiac events, and late mortality. Subgroup analyses were performed for studies published before and after the year 2000 and for the type of risk adjustment. RESULTS: Eighty-four studies were included with a total of 903 346 patients. Females were at higher risk for operative mortality (odds ratio: 1.77, 95% confidence interval [CI]: 1.64-1.92, P < 0.001). At subgroup analysis, there was no difference in operative or late mortality between studies published prior and after 2000 or between studies using risk adjustment. Females were at a higher risk of late mortality (incidence rate ratio [IRR]: 1.16, 95% CI: 1.06-1.26, P < 0.001), major adverse cardiac events (IRR: 1.40, 95% CI: 1.19-1.66, P < 0.001), myocardial infarction (IRR: 1.28, 95% CI: 1.13-1.45, P < 0.001) and stroke (IRR: 1.31, 95% CI: 1.15-1.51, P > 0.001) but not repeat revascularization (IRR: 0.99, 95% CI: 0.76-1.29, P = 0.95). The use of the off-pump technique or multiple arterial grafts was not associated with the primary outcome. CONCLUSIONS: Females undergoing CABG are at higher risk for operative and late mortality as well as postoperative events including major adverse cardiac events, myocardial infarction and stroke. PROSPERO REGISTRATION: CRD42020187556.

Midline Rotation of the Right Renal Hilum During Hand-Assisted Laparoscopic Living Donor Nephrectomy.

BACKGROUND/OBJECTIVES: Laparoscopic living donor nephrectomy (LLDN) of the right kidney is currently considered as part of standard of care; however, dealing with the renal hilum when performing ligation/division of its renal vessels is still a main concern. Here, we describe a simple-to-perform technique, i.e., flipping the fully mobilized right kidney to the midline so that the renal artery becomes anteriorly, which offers better visualization and easier dissection of the renal vessels (achieving maximized lengths) when performing hand-assisted LLDN of the right kidney. METHODS: Living donors who underwent hand-assisted LLDN of the right kidney, along with their respective renal transplant recipients, were included in this report. Donor characteristics included renal artery and vein lengths; recipient characteristics included creatinine at months 12 - 36. Graft vein and arterial anastomosis data were also reported. RESULTS: Nineteen living donors and 19 recipients, with median donor and recipient ages being 39 (24 - 60) and 53 (3 - 81) years, respectively, were included. None of the 38 patients had intra- or postoperative complications. Donor renal vein was anastomosed to the right external iliac vein (n = 16), right common iliac vein (n = 2), and inferior vena cava (n = 1). Gonadal vein (n = 1) and deceased donor iliac vein (n = 2) were used to increase the right renal vein length in 3 cases. Four donor kidneys had 2 arteries reconstructed side by side. None of the recipients developed any vascular or urological complications. CONCLUSIONS: The laparoscopic technique described is safe and allows better visualization of the right hilum, mainly the renal artery, and helps in stapling the renal vein and renal artery.

Case Report: Uroenteric Fistula in a Pediatric-en-bloc Kidney Transplant Manifests as Deceptive Watery Diarrhea and Normal Anion Gap Acidosis.

Introduction: The diagnosis of a post-surgical uroenteric fistula can be challenging and may be delayed for months after symptoms begin. A normal anion gap metabolic acidosis has been reported in up to 100% of patients after ureterosigmoidostomy, and bladder substitution using small bowel and/or colonic segments. Here, we describe a rare case of a pediatric patient who developed a uroenteric fistula from the transplant ureters into the small bowel, after an en-bloc kidney transplantation resulting in profound acidosis and deceptive watery diarrhea. Case Presentation: The patient is an 8-year-old girl with end stage kidney disease (ESKD) secondary to focal segmental glomerulosclerosis. Through a right retroperitoneal approach, she underwent a right native nephrectomy and a pediatric deceased donor en-bloc kidney transplant including two separate ureters. One month later, she had a renal allograft biopsy for suspected rejection. During the week after the biopsy, she experienced abdominal pain followed by watery diarrhea and metabolic acidosis requiring continuous bicarbonate/acetate infusions. An extensive gastro-intestinal evaluation for the cause of the diarrhea including endoscopy was inconclusive. The urine output decreased to <500 ml daily; although, the kidney function remained normal. After 2 weeks of unexplained watery diarrhea a magnetic resonance urogram with contrast was performed which demonstrated extravasation of urine from both ureters with fistulization into the small bowel. She underwent corrective surgery which identified the fistulous tract, which was resected and both ureters were re-implanted. The diarrhea and acidosis resolved, and she has maintained normal renal allograft function for over 1 year. Conclusion: An important aspect in the early diagnosis of a uroenteric fistula is the sudden onset of severe hyperchloremic metabolic acidosis that results when urine is diverted into the intestinal tract. The mechanism is similar to that described in cases of urinary diversions and/or bladder augmentation using the intestine. Important diagnostic tools are the measurements of solute excretion and pH in the urine as compared to the "watery diarrhea" or bowel output. Summary: We describe a case of a uroenteric fistula in a pediatric-en-bloc kidney transplant patient that went undiagnosed for almost 3 weeks due to the deceptive nature of the watery diarrhea which was actually urine. A uroenteric fistula should be considered in the differential diagnosis of diarrhea and hyperchloremic metabolic acidosis as a complication of kidney transplant. The simultaneous comparison of stool and urine pH and solute excretions may lead to the diagnosis, appropriate imaging and surgical intervention.

No Benefit of Prophylactic Surgical Drainage in Combined Liver and Kidney Transplantation: Our Experience and Review of the Literature.

Background: Contrasting results have emerged from limited studies investigating the role of prophylactic surgical drainage in preventing wound morbidity after liver and kidney transplantation. This retrospective study analyzes the use of surgical drain and the incidence of wound complications in combined liver and kidney transplantation (CLKTx). Methods: A total of 55 patients aged ≥18 years were divided into two groups: the drain group (D) (n = 35) and the drain-free group (DF) (n = 20). Discretion to place a drain was based exclusively on surgeon preference. All deceased donor kidneys were connected to the LifePort Renal Preservation Machine® prior to transplantation, in both simultaneous and delayed technique of implantation of the renal allograft. The primary outcome was the development of superficial/deep wound complications during the study follow-up. Secondary outcomes included the development of delayed graft function (DGF) of the transplanted kidney, primary non-function (PNF) and early allograft dysfunction (EAD) of the transplanted liver, graft failure, graft and patient survival, overall post-operative morbidity rate and length of hospital stay. Results: With a median follow-up of 14.4 months after transplant, no difference in the incidence of superficial/deep wound complications, except for hematomas, in collections size, intervention rate, PNF, EAD, graft failure and patient survival, was observed between the 2 groups. Significantly lower level of platelets, higher INR values, DGF, morbidity rates and length of hospital stay were reported post-operatively in the D group. Pre-operative hypoalbuminemia and longer CIT were included in the propensity score for receiving a drain and were associated with a significantly higher rate of developing a hematoma post-transplant. Conclusions: Absence of the surgical drain did not appear to adversely affect wound morbidity compared to the prophylactic use of drains in renal transplant patients during CLKTx.

Characteristics of Randomized Clinical Trials in Surgery From 2008 to 2020: A Systematic Review.

Importance: Randomized clinical trials (RCTs) provide the highest level of evidence to evaluate 2 or more surgical interventions. Surgical RCTs, however, face unique challenges in design and implementation. Objective: To evaluate the design, conduct, and reporting of contemporary surgical RCTs. Evidence Review: A literature search performed in the 2 journals with the highest impact factor in general medicine as well as 6 key surgical specialties was conducted to identify RCTs published between 2008 and 2020. All RCTs describing a surgical intervention in both experimental and control arms were included. The quality of included data was assessed by establishing an a priori protocol containing all the details to extract. Trial characteristics, fragility index, risk of bias (Cochrane Risk of Bias 2 Tool), pragmatism (Pragmatic Explanatory Continuum Indicator Summary 2 [PRECIS-2]), and reporting bias were assessed. Findings: A total of 388 trials were identified. Of them, 242 (62.4%) were registered; discrepancies with the published protocol were identified in 81 (33.5%). Most trials used superiority design (329 [84.8%]), and intention-to-treat as primary analysis (221 [56.9%]) and were designed to detect a large treatment effect (50.0%; interquartile range [IQR], 24.7%-63.3%). Only 123 trials (31.7%) used major clinical events as the primary outcome. Most trials (303 [78.1%]) did not control for surgeon experience; only 17 trials (4.4%) assessed the quality of the intervention. The median sample size was 122 patients (IQR, 70-245 patients). The median follow-up was 24 months (IQR, 12.0-32.0 months). Most trials (211 [54.4%]) had some concern of bias and 91 (23.5%) had high risk of bias. The mean (SD) PRECIS-2 score was 3.52 (0.65) and increased significantly over the study period. Most trials (212 [54.6%]) reported a neutral result; reporting bias was identified in 109 of 211 (51.7%). The median fragility index was 3.0 (IQR, 1.0-6.0). Multiplicity was detected in 175 trials (45.1%), and only 35 (20.0%) adjusted for multiple comparisons. Conclusions and Relevance: In this systematic review, the size of contemporary surgical trials was small and the focus was on minor clinical events. Trial registration remained suboptimal and discrepancies with the published protocol and reporting bias were frequent. Few trials controlled for surgeon experience or assessed the quality of the intervention.

Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation: A retrospective, single center study.

BACKGROUND: There is an abundant need to increase the availability of deceased donor kidney transplantation (DDKT) to address the high incidence of kidney failure. Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients; thus the identification of modifiable risk factors associated with poor outcomes is paramount. AIM: To identify risk factors associated with delayed graft function (DGF). METHODS: Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients. The primary outcome was the occurrence of DGF. RESULTS: The incidence of DGF was 27%. Under logistic regression, eight independent risk factors for DGF were identified including recipient body mass index ≥ 30 kg/m2, baseline mean arterial pressure < 110 mmHg, intraoperative phenylephrine administration, cold storage time ≥ 16 h, donation after cardiac death, donor history of coronary artery disease, donor terminal creatinine ≥ 1.9 mg/dL, and a hypothermic machine perfusion (HMP) pump resistance ≥ 0.23 mmHg/mL/min. CONCLUSION: We delineate the association between DGF and recipient characteristics of pre-induction mean arterial pressure below 110 mmHg, metabolic syndrome, donor-specific risk factors, HMP pump parameters, and intraoperative use of phenylephrine.

When is it safe to perform abdominal transplantation in patients with prior SARS-CoV-2 infection: A case series.

BACKGROUND: The Coronavirus disease 2019(COVID-19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS-CoV-2 infection. A full understanding of this scenario is required, as transplantation is a life-saving procedure and COVID-19 remains an ongoing threat. METHODS: Abdominal organ transplant recipients diagnosed with COVID-19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post-transplant. RESULTS: We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS-CoV-2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow-up was 79 (22-190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow-up, only one patient developed rejection; thirteen patients had favorable graft outcomes. CONCLUSIONS: We were able to perform abdominal transplantation for patients with COVID-19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS-CoV-2 infection.

Safety and Efficacy of Evacetrapib in Patients with Inadequately-controlled Hypercholesterolemia and High Cardiovascular Risk; A meta-analysis of Randomized Placebo-controlled Trials.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is causally related to cardiovascular disease. Inhibition of cholesteryl ester transfer protein with Evacetrapib may provide an additional treatment option for patients who do not reach their LDL-C goal with statins or patients who cannot tolerate statins. We aimed to evaluate the safety and efficacy of Evacetrapib in patients with inadequately-controlled hypercholesterolemia and high cardiovascular risk. METHOD: A computer literature search for PubMed, Scopus, and Science Direct was carried out from inception to 2019 and was updated from January 2019 till March 2021. We included only RCTs. Data were pooled as a mean difference in a random-effect model using the Mantel-Haenzel (M-H) method. We used Open Meta [Analyst] software (by the center of evidence-based medicine, Oxford University, UK). RESULTS: Five studies (n = 12,937 patients) reported in five articles were included in this meta-analysis. The overall pooled estimate showed that LDL-C was significantly lower in the evacetrapib group than the placebo group (MD -34.07 mg/dL, 95% CI [-40.66, -27.49], p<0.0001). The pooled estimate showed that Apo-B was significantly lower in the evacetrapib130 mg group than the placebo group (MD -22.64 mg/dL, 95% CI [-30.70, -14.58], p<0.0001). HDL-C was significantly higher in the evacetrapib group over the placebo group (MD 93.31 mg/dL, 95% CI [56.07, 130.56], p<0.0001). CONCLUSION: Current evidence from five RCTs (12,539 participants) suggests that evacetrapib has favorable outcomes in patients with inadequately-controlled Hypercholesterolemia and high cardiovascular risks. Evacetrapib could significantly increase the HDL and Apo-A1 levels and lower the LDL cholesterol and Apo-B levels with an acceptable safety profile.

Cyclosporine Lipid Nanocapsules as Thermoresponsive Gel for Dry Eye Management: Promising Corneal Mucoadhesion, Biodistribution and Preclinical Efficacy in Rabbits.

An ophthalmic cyclosporine (CsA) formulation based on Lipid nanocapsules (LNC) was developed for dry eye management, aiming to provide targeting to ocular tissues with long-term drug levels and maximum tolerability. CsA-LNC were of small particle size (41.9 ± 4.0 nm), narrow size distribution (PdI ≤ 0.1), and high entrapment efficiency (above 98%). Chitosan (C) was added to impart positive charge. CsA-LNC were prepared as in-situ gels using poloxamer 407 (P). Ex vivo mucoadhesive strength was evaluated using bovine cornea, while in vivo corneal biodistribution (using fluorescent DiI), efficacy in dry eye using Schirmer tear test (STT), and ocular irritation using Draize test were studied in rabbits compared to marketed ophthalmic CsA nanoemulsion (CsA-NE) and CsA in castor oil. LNC incorporation in in-situ gels resulted in an increase in mucoadhesion, and stronger fluorescence in corneal layers seen by confocal microscopy, compared to the other tested formulations. Rate of recovery (days required to restore corneal baseline hydration level) assessed over 10 days, showed that CsA-LNC formulations produced complete recovery by day 7 comparable to CsA-NE. No Ocular irritation was observed by visual and histopathological examination. Based on data generated, CsA-LNC-CP in-situ gel proved to be a promising effective nonirritant CsA ophthalmic formulation for dry eye management.