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Background: Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. Methods: We studied 50 kidney transplant recipients following SARS‐CoV‐2 vaccination and quantified their anti‐spike protein antibody, donor‐derived cell‐free DNA (dd‐cfDNA), gene expression profiling (GEP), and alloantibody formation. Results: Participants were stratified using nucleocapsid testing as either SARS‐CoV‐2‐naïve or experienced prior to vaccination. One of 34 (3%) SARS‐CoV‐2 naïve participants developed anti‐spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS‐CoV‐2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre‐ and post‐vaccination levels did not change for median dd‐cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de‐novo donor specific antibody status, or estimated glomerular filtration rate. Conclusions: SARS‐CoV‐2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

The importance of measuring trust in health systems has been accentuated due to its correlation with important health outcomes aimed at reducing COVID‐19 transmission. A systematic review published almost a decade ago identified gaps in measures including the lack of focus on trust in systems, inconsistency regarding the dimensionality of trust and need for research to strengthen the validity of measures. Given developments in our understandings of trust since its publication, we sought to identify new scales developed, existing ones adapted in response to identified gaps, and agendas for future research. Using the PRISMA approach for systematic reviews, we conducted a search in four databases. A total of 26 articles were assessed. Twelve new scales were identified, while 14 were adapted for different settings and populations. Literature continues to focus on measuring trust in health professionals rather than systems. Various shortcomings were identified, including some articles not mentioning the dimensions included in the scale and suboptimal use of validity and reliability testing and/or reporting. Moreover, a variety of terms were used for dimensions. Future research is needed to address these gaps and consequently, to understand their correlation with health behaviors and outcomes more accurately. [ABSTRACT FROM AUTHOR]

Objective: To evaluate seroreactivity and disease flares after COVID‐19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). Methods: Ninety SLE patients and 20 healthy controls receiving a complete COVID‐19 vaccine regimen were included. IgG seroreactivity to the SARS–CoV‐2 spike receptor‐binding domain (RBD) and SARS–CoV‐2 microneutralization were used to evaluate B cell responses; interferon‐γ (IFNγ) production was measured by enzyme‐linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment–SLEDAI flare index. Results: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS–CoV‐2 spike RBD compared to fully vaccinated controls. Twenty‐six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti–double‐stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS–CoV‐2 spike RBD strongly correlated with the SARS–CoV‐2 microneutralization titers and correlated with antigen‐specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre‐ and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. Conclusion: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID‐19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination. [ABSTRACT FROM AUTHOR]

However, a third vaccine dose with Ad26.COV2.S vaccine resulted in robust increases in antibody titers, presence of neutralizing antibodies, and an increased frequency of RBD-reactive B cells in circulation. Recent studies demonstrated the standard two-dose regimen of the Pfizer-BioNTech BNT162b2 vaccine could yield suboptimal immune responses and incomplete clinical protection in transplanted patients.2 Semi-quantitative antibody titers for anti-Spike (S) protein receptior-binding domain (RBD) may not fully reflect post-vaccine immune responses. COVID-19 vaccines utilizing mRNA technology induce vigorous immune responses and excellent protection against disease in immunocompetent adults.1 The degree of vaccine efficacy in transplanted individuals remains unknown. [Extracted from the article]

Objectives: To evaluate the effect of a prospective opioid reduction intervention after radical prostatectomy (RP; based on a surgery‐specific guideline and education) on post‐discharge opioid prescribing, use, disposal, and need for additional opioid medication. Patients and Methods: A prospective, non‐randomised, pre–post interventional trial of patients undergoing RP for prostate cancer (August 2017–November 2018) was conducted as part of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative. An evidence‐based intervention including: a discharge sheet, nursing education, and standardised prescribing guideline, was applied with the primary outcome of total oral morphine equivalents (OMEQ) used after RP. Secondary outcomes included opioid prescribing, opioid disposal, need for additional opioid medication, and presence of incisional/post‐surgical abdominal pain at 30 days after RP. Results: A total of 214 (Pre‐Intervention arm) and 229 (Post‐Intervention arm) adult patients were enrolled (100% follow‐up). The intervention reduced post‐discharge opioid prescribing (from 224.3 to 120.3 mg; −46.4%, P = 0.01), reduced opioid use (from 52.1 to 38.3 mg; −26.5%, P < 0.01), and increased opioid disposal (+13.5%, P < 0.01). Greater prescribing of opioids at discharge, higher body mass index, and use of opioid medication prior to surgery, were independently associated with greater post‐discharge opioid use, while history of a chronic pain diagnosis was not statistically significant. In the Post‐Intervention cohort, 2.2% of patients needed additional medication for post‐surgical pain (0.9% obtained a prescription) and 1.3% initiated long‐term use. Conclusions: A prospective, evidence‐based intervention reduced post‐discharge opioid prescribing and use, while increasing disposal after RP. Risk factors for increased opioid use were identified. The results support expanding the use of evidence‐based opioid reduction interventions to other surgical specialties. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Off-clamp laparoscopic partial nephrectomy (LPN) is thought to preserve renal function by limiting warm ischaemia time (WIT) and consequently reperfusion injury. To date, studies using the off-clamp technique represent a heterogeneous group, with limited follow-up showing feasibility and safety in a restricted number of cases. We report the largest experience of off-clamp vs on-clamp LPN with perioperative outcomes and intermediate follow-up of renal functional outcomes with stratification by WIT. OBJECTIVE To evaluate perioperative and 6-month renal functional outcomes of patients undergoing off-clamp vs complete hilar control laparoscopic partial nephrectomy (LPN)., PATIENTS AND METHODS A retrospective review of 489 patients undergoing LPN was completed., Preoperative imaging assessed tumour characteristics., Patient demographics, perioperative parameters, and postoperative outcomes were documented., Multivariable regression analysis was used to assess factors contributing to changes in postoperative renal function between off-clamp and clamped LPN., RESULTS In all, 289 LPNs were performed on-clamp and 150 were performed off-clamp., Tumours in the on-clamp group were larger than those in the off-clamp group (mean [range] 3.3 [0.5-13.5] vs 2.7 [0.4-9] cm, P= 0.003)., Univariable analysis comparing off-clamp to on-clamp cohorts showed that estimated glomerular filtration rate (eGFR) was better preserved in the off-clamp cohort at 6 months (−5.8% vs -11.4%, P= 0.046). Multivariable analysis of the groups showed that estimate blood loss ( P= 0.015) and warm ischaemia time (WIT, P< 0.001) were the only significant predictors of decreased eGFR in the postoperative period., Difference in eGFR at 6 months was not significant when WIT was limited to 30 min. The complication rate was greater in the clamped cohort (10% vs 20%, P= 0.012)., There was no difference in transfusion rate or positive margin status., CONCLUSIONS LPN without hilar clamping is feasible, safe and associated with less renal injury as assessed by postoperative GFR in select patients., With experience, it can be applied to complex renal lesions. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? With the advancement of minimally invasive surgery, the management of small renal masses (SRM) has dramatically changed. Ablative technology such as radiofrequency ablation (RFA) and cryoablation have emerged as viable alternative modalities to extirpative surgery. RFA is one of the most studied and applied energy-based, needle-ablative treatment modalities, with encouraging mid- and long-term oncological outcomes. Monopolar devices have several shortcomings. The electrodes are susceptible to the cooling effect of nearby blood vessels that act as a 'heat sink', limiting the extent of tissue ablation and forming lesions with asymmetric borders and 'skip lesions'. Therefore, it is difficult to monitor and accurately predict the size of ablated lesions. A novel bipolar radiofrequency ablation (BRFA) device has been recently developed to address concerns with monopolar systems (Trod Medical, Paris, France). The BRFA system addresses the limitations of monopolar RFA, in terms of lesion size, targeting, consistency and concerns about cell death in the ablated area. We evaluated the BRFA device in 10 patients undergoing laparoscopic partial or radical nephrectomy. The present study demonstrates the safety and efficacy of a novel BRFA device. A BRFA device can produce a defined reproducible lesion with a precise transition zone to normal tissue. The area of ablated tissue exhibited completely devitalized cells and precise transition zone. With these characteristics, the potential advantages of this new technology during RFA ablation of SRM include less collateral damage and more complete ablation without skip lesions. This has the potential to lower rates of local recurrence and reduce incidence of skin burns. Further follow-up studies are necessary to determine its oncological efficacy. OBJECTIVE To evaluate a novel bipolar radiofrequency ablation (BRFA) system for the destruction of kidney tumours in patients., MATERIALS AND METHODS Bipolar radiofrequency ablation (BRFA) was used to ablate renal masses in 10 patients undergoing laparoscopic radical or partial nephrectomy., The probe was placed percutaneously and laparoscopically guided into the tumour after routine laparoscopic exposure. The electrical current was continuously adjusted by the generator to overcome disruption from increasing impedance created from desiccated tissue., The specimens were then excised in routine fashion and analysed by a single pathologist., Lesion size and shape, and size of the transition zone to viable tissue were measured via nicotinamide adenine dinucleotide (NADH) staining., RESULTS Ablation was successful in all 10 tumours. Mean time to set up and place the probe was between 2 and 4 min. Duration of ablation was 200 s., None of the ablated tissue showed signs of viable cells by histological examination and NADH staining., The mean size of the ablation zone was 6.26 cm3, with regular borders and a tapered cylindrical shape similar to the shape of the outer coil., The width of the transition zone, or area spanning complete tissue ablation to the first viable cells, ranged from 10 to 60 µm., There were no complications noted due to the ablation., CONCLUSIONS A BRFA device can produce a defined reproducible lesion with a precise transition zone to normal tissue., The area of ablated tissue exhibited completely devitalized cells and precise transition zone. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Minimizing renal ischemia and reperfusion injury is an area of active investigation and is particularly significant in cases of laparoscopic renal surgery where the kidney experiences warm ischemia. Reports of partial clamping, early unclamping, and off-clamp laparoscopic partial nephrectomy have demonstrated potential technical modifications that can offer a protective role in preserving renal function. We investigated off-clamp laparoscopic partial nephrectomy for tumours with varying clinical stage to determine feasibility, perioperative outcomes, and renal functional changes when compared to a contemporary cohort of standard laparoscopic partial nephrectomy with complete hilar clamping performed by a single surgeon. OBJECTIVE To compare the operative outcomes and oncological efficacy of off-clamp (OC) laparoscopic partial nephrectomy (LPN) vs complete hilar control (HC) LPN for stage T1a-T2 renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Study Type - Diagnostic (symptom prevalence) Level of Evidence 2b What's known on the subject? and What does the study add? Symptom variability is profound in the population of patients diagnosed with interstitial cystitis and painful bladder syndrome because these diagnoses represent a very heterogeneous patient population. Recently, younger patients are being diagnosed with these pain syndromes, without any specific investigation into the symptoms they experience. We identified that patients diagnosed with interstitial cystitis and painful bladder syndrome have variable clinical symptom profiles depending on the age at the time of their diagnosis. Dyspareunia, external genitalia pain, urgency, frequency and dysuria were more common in younger patients whereas nocturia, urinary incontinence and the presence of Hunner's ulcers were more common in older patients. Better defining symptom profiles for patients at the time of evaluation may potentially aid in more accurate and expedited diagnosis of these conditions, particularly in the youngest patient population which is being recognized more commonly in recent times. OBJECTIVE To investigate the clinical profile differences among patients with interstitial cystitis/painful bladder syndrome (IC/PBS) based upon age at the time of diagnosis from childhood into the geriatric age group. [ABSTRACT FROM AUTHOR]

The article provides information on the replication of surgical innovation process as portrayed in Tom Wolfe's novel, "The Electric Kool-Aid Acid Test". It discusses the surgical invention in the past including that from Max Nitze, Thomas Edison and George Kelling. The surgical procedures continue to develop as older modalities are applied in unconventional ways such as the approaches of natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single-site surgery (LESS).

Background Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease due to α-L-iduronidase (IDUA) deficiency that results in the accumulation of glycosaminoglycans (GAG). Gene therapy can reduce most clinical manifestations, but mice that receive transfer as adults lose expression unless they receive immunosuppression. Increasing liver specificity of transgene expression has reduced immune responses to other genes. Methods A gamma retroviral vector was generated with a liver-specific human α1-antitrypsin promoter and the canine IDUA cDNA inverted relative to the retroviral long-terminal repeat. Adult MPS I mice received the vector intravenously at 6 weeks of age and were assessed for expression via serial serum IDUA assays. Functional testing and organ analysis were performed at 8 months. Results This vector resulted in high specificity of expression in liver, and serum IDUA activity was stable in 90% of animals. Although the average serum IDUA activity was relatively low at 12.6 ± 8.1 units/ml in mice with stable expression, a relatively high percentage of enzyme contained the mannose 6-phosphorylation necessary for uptake by other cells. At 6.5 months after transduction, most organs had high IDUA activity and normalized GAG levels. There was complete correction of hearing and vision abnormalities and significant improvements in bone, although the aorta was refractory to treatment. Conclusions Stable expression of IDUA in adult MPS I mice can be achieved without immunosuppression by modifying the vector to reduce expression in the spleen. This approach may be effective in patients with MPS I or other lysosomal storage diseases. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 OBJECTIVE • To determine the pressure-flow characteristics of neobladders created in various configurations that may be constructed intra-abdominally. Complete intracorporeal neobladder construction has been previously described but is limited due to excessive operative time and the need for an advanced laparoscopic skill set. MATERIALS AND METHODS • Four neobladder configurations were constructed, each using 20 cm of human cadaveric small intestine. The standard hand sewn Studer pouch was compared with a circular loop, W-pouch, and U-pouch with stapled anastamoses. • Pressure flow studies were completed using the Aquarius TT UDS system (Laborie Medical Technologies, Toronto, Ontario) and each neobladder was filled to a pressure of 50 cm H2O. Neobladder change in pressure, capacity, and overall compliance were determined. RESULTS • The cystometric capacities of the stapled U-pouch, W-pouch, Circle pouch, and Studer pouch were 167.3 mL, 177.5 mL, 114 mL, and 145.2 mL respectively. The first increase in intravesical pressure was at 90.3 mL, 103 mL, 50 mL, and 85 mL. • The greatest compliance of 3.81 mL/cmH2O was demonstrated in the U-pouch, with the W-pouch revealing a compliance of 3.44 mL/cmH2O. • The least compliant neobladder was the circle pouch (2.24 mL/cmH20) followed by the standard Studer pouch (2.94 mL/cmH2O). CONCLUSION • The construction of an orthotopic neobladder must not only be technically feasible but maintain adequate capacity and compliance for optimal functioning. Pressure-flow studies demonstrated equivalent results in alternate neobladder configurations. Additional data is needed to determine feasibility in vivo. [ABSTRACT FROM AUTHOR]