Search

Background: Weight recurrence (WR) affects nearly 20% of patients after bariatric surgery and may decrease its benefits, affecting patients' quality of life negatively. Patient perspectives on WR are not well known. Objectives: Assess patient needs, goals, and preferences regarding WR treatment. Setting: Single MBSAQIP-accredited academic center, and online recruitment. Methods: An 18-item, web-based survey was distributed to adults seeking treatment for WR after a primary bariatric surgery (PBS), in addition to online recruitment, between 2021 and 2023. Survey items included somatometric data, questions about the importance of factors for successful weight loss, procedure decision-making, and treatment expectations. Results: Fifty-six patients with > 10% increase from their nadir weight were included in the study. Patients had initially undergone Roux-en-Y gastric bypass (62.5%), sleeve gastrectomy (28.6%), adjustable gastric banding (3.6%), or other procedures (5.3%). When assessing their satisfaction with PBS, 57.1% were somewhat/extremely satisfied, 33.9% somewhat/extremely dissatisfied, while 8.9% were ambivalent. Patients considered the expected benefits (for example, weight loss) as the most important factor when choosing a treatment option for WR. Patient goals included "feeling good about myself" (96.4% very/extremely important), "being able to resume activities I could not do before" (91% very/extremely important), and "improved quality of life" and "-life expectancy" (> 90% very/extremely important). Finally, RBS, lifestyle modification with peer support, and anti-obesity medication were ranked as first treatment options for WR by 40%, 38.8%, and 29.8% of the respondents, respectively. Conclusions: Patients considered weight loss as the most important factor when choosing treatment modality for WR, with RBS and lifestyle changes being preferred over weight-loss medications. Large prospective randomized trials are needed to counsel this patient population better. [ABSTRACT FROM AUTHOR]

Background: Excess tumor necrosis factor (TNF) is implicated in the pathogenesis of hyperinflammatory experimental cerebral malaria (eCM), including gliosis, increased levels of fibrin(ogen) in the brain, behavioral changes, and mortality. However, the role of TNF in eCM within the brain parenchyma, particularly directly on neurons, remains underdefined. Here, we investigate electrophysiological consequences of eCM on neuronal excitability and cell signaling mechanisms that contribute to observed phenotypes. Methods: The split-luciferase complementation assay (LCA) was used to investigate cell signaling mechanisms downstream of tumor necrosis factor receptor 1 (TNFR1) that could contribute to changes in neuronal excitability in eCM. Whole-cell patch-clamp electrophysiology was performed in brain slices from eCM mice to elucidate consequences of infection on CA1 pyramidal neuron excitability and cell signaling mechanisms that contribute to observed phenotypes. Involvement of identified signaling molecules in mediating behavioral changes and sickness behavior observed in eCM were investigated in vivo using genetic silencing. Results: Exploring signaling mechanisms that underlie TNF-induced effects on neuronal excitability, we found that the complex assembly of fibroblast growth factor 14 (FGF14) and the voltage-gated Na+ (Nav) channel 1.6 (Nav1.6) is increased upon tumor necrosis factor receptor 1 (TNFR1) stimulation via Janus Kinase 2 (JAK2). On account of the dependency of hyperinflammatory experimental cerebral malaria (eCM) on TNF, we performed patch-clamp studies in slices from eCM mice and showed that Plasmodium chabaudi infection augments Nav1.6 channel conductance of CA1 pyramidal neurons through the TNFR1–JAK2–FGF14–Nav1.6 signaling network, which leads to hyperexcitability. Hyperexcitability of CA1 pyramidal neurons caused by infection was mitigated via an anti-TNF antibody and genetic silencing of FGF14 in CA1. Furthermore, knockdown of FGF14 in CA1 reduced sickness behavior caused by infection. Conclusions: FGF14 may represent a therapeutic target for mitigating consequences of TNF-mediated neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: Acute cholecystitis (AC) is one of the most prevalent diseases in clinical practice. Poor surgical candidates may benefit from early percutaneous cholecystostomy (PC) drainage followed by interval cholecystectomy (IC), which is the definitive treatment. The optimal timing between the PC drainage and the IC has not been identified. This study aimed to investigate how the duration between PC and IC affects perioperative outcomes and identify the optimal IC timing to minimize complications. Methods: This retrospective cohort study included all adult patients diagnosed with AC who underwent PC followed by IC at a single institution center between 2014 and 2022. Patients with a history of hepatobiliary surgery, stones in the common bile duct, cirrhosis, active malignancy, or prolonged immunosuppression were excluded. The analysis did not include cases with major concurrent procedures during cholecystectomy, previously aborted cholecystectomies, or failure of the PC drain to control the inflammation. Linear and logistic regression models were used to analyze the impact of the interval between PC and IC on intra- and perioperative outcomes. Results: One hundred thirty-two patients (62.1% male) with a mean age of 64.4 ± 15 (mean ± SD) years were diagnosed with AC (25% mild, 47.7% moderate, 27.3% severe). All patients underwent PC followed by IC after a median of 64 [48–91] days. Longer ICU stay was associated with longer time intervals between PC and IC (Coef 105.98, p < 0.001). No significant variations were detected in the intraoperative and perioperative outcomes between patients undergoing IC within versus after 8 weeks from PC placement. However, a higher percentage of patients with delayed IC (after 8 weeks) were discharged home (96.4% vs. 83.7%; p = 0.019). Conclusions: Patients may benefit from undergoing IC after the 8-week cutoff after PC. However, very long periods between PC and IC procedures may increase the risk of longer ICU stay. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency anemia is a common paraesophageal hernia (PEH) symptom and may improve after repair. When present, anemia has also been proposed to be associated with an increase in length of hospital stay, morbidity, and mortality after PEH repair. This study aimed to determine anemia-related factors in patients with PEH, the rate of anemia resolution after PEH repair, and the risk of anemia recurrence when repair failed. Methods: We included patients who received a PEH repair between June 2019 and June 2020 and had 24 months of postoperative follow-up. Demographics and comorbidities were recorded. Anemia was defined as pre-operative hemoglobin values < 12.0 for females and < 13.0 for males, or if patients were receiving iron supplementation. Anemia resolution was determined at 6 months post-op. Length of hospital stay, morbidity, and mortality was recorded. Logistic regression and ANCOVA were used for binary and continuous outcomes respectively. Results: Of 394 patients who underwent PEH repair during the study period, 101 (25.6%) had anemia before surgery. Patients with pre-operative anemia had larger hernia sizes (6.55 cm ± 2.77 vs. 4.34 cm ± 2.50; p < 0.001). Of 68 patients with available data by 6 months after surgery, anemia resolved in 36 (52.9%). Hernia recurred in 6 patients (16.7%), 4 of whom also had anemia recurrence (66.7%). Preoperative anemia was associated with a higher length of hospital stay (3.31 days ± 0.54 vs 2.33 days ± 0.19 p = 0.046) and an increased risk of post-operative all-cause mortality (OR 2.7 CI 1.08–6.57 p = 0.05). Fundoplication type (p = 0.166), gastropexy, or mesh was not associated with an increased likelihood of resolution (OR 0.855 CI 0.326–2.243; p = 0.05) (OR 0.440 CI 0.150–1.287; p = 0.05). Conclusions: Anemia occurs in 1 out of 4 patients with PEH and is more frequent in patients with larger hernias. Anemia is associated with a longer hospital stay and all-cause mortality after surgery. Anemia recurrence coincided with hernia recurrence in roughly two-thirds of patients. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common cause of dementia and is classically characterized by two major histopathological abnormalities: extracellular plaques composed of amyloid beta (Aβ) and intracellular hyperphosphorylated tau. Due to the progressive nature of the disease, it is of the utmost importance to develop disease-modifying therapeutics that tackle AD pathology in its early stages. Attenuation of hippocampal hyperactivity, one of the earliest neuronal abnormalities observed in AD brains, has emerged as a promising strategy to ameliorate cognitive deficits and abate the spread of neurotoxic species. This aberrant hyperactivity has been attributed in part to the dysfunction of voltage-gated Na+ (Nav) channels, which are central mediators of neuronal excitability. Therefore, targeting Nav channels is a promising strategy for developing disease-modifying therapeutics that can correct aberrant neuronal phenotypes in early-stage AD. This review will explore the role of Nav channels in neuronal function, their connections to AD pathology, and their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Objectives To identify the long-term sexual health outcomes and relationships in men born with classic bladder exstrophy ( CBE). Materials and Methods A prospectively maintained institutional database comprising 1248 patients with exstrophy-epispadias was used. Men aged ≥18 years with CBE were included in the study. A 42-question survey was designed using a combination of demographic information and previously validated questionnaires. Results A total of 215 men met the inclusion criteria, of whom 113 (53%) completed the questionnaire. The mean age of the respondents was 32 years. Ninety-six (85%) of the respondents had been sexually active in their lifetime, and 66 of these (58%) were moderately to very satisfied with their sex life. The average Sexual Health Inventory for Men score was 19.8. All aspects of assessment using the Penile Perception Score questionnaire were on average between 'very dissatisfied' and 'satisfied'. Thirty-two respondents (28%) had attempted to conceive with their partner. Twenty-three (20%) were successful in conceiving, while 31 (27%) reported a confirmed fertility problem. A total of 31 respondents (27%) reported undergoing a semen analysis or post-ejaculatory urine analysis. Of these, only four respondents reported azoospermia. Conclusion Patients with CBE have many of the same sexual and relationship successes and concerns as the general population. This is invaluable information to give to both the parents of boys with CBE, and to the boys themselves as they transition to adulthood. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the effect of TeamSTEPPS on operating room efficiency and patient safety. TeamSTEPPS consisted of briefings attended by all health care personnel assigned to the specific operating room to discuss issues unique to each case scheduled for that day. The operative times, on-time start rates, and turnover times of all cases performed by the urology service during the initial year with TeamSTEPPS were compared to the prior year. Patient safety issues identified during postoperative briefings were analyzed. The mean case time was 12.7 minutes less with TeamSTEPPS (P < .001). The on-time first-start rate improved by 21% with TeamSTEPPS (P < .001). The mean room turnover time did not change. Patient safety issues declined from an initial rate of 16% to 6% at midyear and remained stable (P < 0.001). TeamSTEPPS was associated with improved operating room efficiency and diminished patient safety issues in the operating room. [ABSTRACT FROM AUTHOR]

Background and Purpose: Liposomal bupivacaine is a delayed-release preparation providing up to 72 hours of local analgesia. It costs much more than standard bupivacaine, however. A prospective, randomized, patient-blinded, controlled trial was performed to assess the efficacy of liposomal bupivacaine versus 0.25% bupivacaine when injected into surgical incisions during laparoscopic and robot-assisted urologic surgery. Methods: A total of 206 adults were randomized to receive liposomal bupivacaine or 0.25% bupivacaine. All surgical incisions were injected with liposomal bupivacaine or 0.25% bupivacaine with systematic dosing. The primary outcome was total opioid consumption during the postoperative hospital stay. All opioid doses were converted to morphine equivalents. Secondary end points included pain scores using visual analog pain scales, duration of hospital stay, and the time to first opioid use. A subgroup analysis was performed for renal surgery patients. Results: There was no significant difference in median total opioid use during the hospital stay between those who received liposomal bupivacaine (15 [interquartile range (IQR) 6.7-27] mg) and 0.25% bupivacaine (17.3 [IQR 8.3-30.5] mg) ( P=0.39). Furthermore, pain scores, length of hospital stay, and time to first opioid use did not differ between groups. Subgroup analysis of laparoscopic renal surgery revealed no difference between liposomal bupivacaine and 0.25% bupivacaine. Conclusions: For laparoscopic and robot-assisted urologic surgery, there is no significant difference between liposomal bupivacaine and 0.25% bupivacaine for local analgesia at the incision sites. [ABSTRACT FROM AUTHOR]

Purpose: To determine predictors of fluoroscopy time during uncomplicated, unilateral ureteroscopy for urolithiasis performed by urology residents during the first 2 years of residency. Methods: The patient charts and computed tomography scans of consecutive, unilateral, uncomplicated ureteroscopy cases for urolithiasis were retrospectively reviewed. The cases were performed by beginning urology residents over the course of their first 2 years of urology residency training. Results: A total of 200 ureteroscopy cases were reviewed. The mean stone diameter was 7.1 (±3.2) mm. Forty-three percent of cases were performed for renal stones and 58 % for ureteral stones. The mean operative time was 80.2 (±36.9) min. The mean fluoroscopy time was 69.1 (±38.2) s. No significant differences existed between cases performed by each of the two residents, and no statistical differences in case difficulty were observed throughout the study period. Linear regression analysis revealed the strongest association with lower fluoroscopy time to be increasing resident experience ( p < 0.001). By the end of the 2-year review, fluoroscopy time decreased by 79 % from 135 to 29 s per case. Other significant factors associated with increasing fluoroscopy time were placement of a postoperative stent under fluoroscopic guidance ( p < 0.001), utilization of a flexible ureteroscope as opposed to a semirigid ureteroscope ( p < 0.001), and balloon dilation of the ureteral orifice ( p < 0.001). Conclusions: Fluoroscopy time during uncomplicated, unilateral ureteroscopy for urolithiasis decreases with increasing urology resident operative experience. Other technical options during ureteroscopy were also found to influence fluoroscopy time. [ABSTRACT FROM AUTHOR]

Voltage-gated Na+ (Nav) channels are the primary molecular determinant of the action potential. Among the nine isoforms of the Nav channel α subunit that have been described (Nav1.1-Nav1.9), Nav1.1, Nav1.2, and Nav1.6 are the primary isoforms expressed in the central nervous system (CNS). Crucially, these three CNS Nav channel isoforms display differential expression across neuronal cell types and diverge with respect to their subcellular distributions. Considering these differences in terms of their localization, the CNS Nav channel isoforms could represent promising targets for the development of targeted neuromodulators. However, current therapeutics that target Nav channels lack selectivity, which results in deleterious side effects due to modulation of off-target Nav channel isoforms. Among the structural components of the Nav channel α subunit that could be pharmacologically targeted to achieve isoform selectivity, the C-terminal domains (CTD) of Nav channels represent promising candidates on account of displaying appreciable amino acid sequence divergence that enables functionally unique protein–protein interactions (PPIs) with Nav channel auxiliary proteins. In medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a critical brain region of the mesocorticolimbic circuit, the PPI between the CTD of the Nav1.6 channel and its auxiliary protein fibroblast growth factor 14 (FGF14) is central to the generation of electrical outputs, underscoring its potential value as a site for targeted neuromodulation. Focusing on this PPI, we previously developed a peptidomimetic derived from residues of FGF14 that have an interaction site on the CTD of the Nav1.6 channel. In this work, we show that whereas the compound displays dose-dependent effects on the activity of Nav1.6 channels in heterologous cells, the compound does not affect Nav1.1 or Nav1.2 channels at comparable concentrations. In addition, we show that the compound correspondingly modulates the action potential discharge and the transient Na+ of MSNs of the NAc. Overall, these results demonstrate that pharmacologically targeting the FGF14 interaction site on the CTD of the Nav1.6 channel is a strategy to achieve isoform-selective modulation, and, more broadly, that sites on the CTDs of Nav channels interacted with by auxiliary proteins could represent candidates for the development of targeted therapeutics. [ABSTRACT FROM AUTHOR]

Voltage-gated Na+ (Nav) channels are a primary molecular determinant of the action potential (AP). Despite the canonical role of the pore-forming α subunit in conferring this function, protein–protein interactions (PPI) between the Nav channel α subunit and its auxiliary proteins are necessary to reconstitute the full physiological activity of the channel and to fine-tune neuronal excitability. In the brain, the Nav channel isoforms 1.2 (Nav1.2) and 1.6 (Nav1.6) are enriched, and their activities are differentially regulated by the Nav channel auxiliary protein fibroblast growth factor 14 (FGF14). Despite the known regulation of neuronal Nav channel activity by FGF14, less is known about cellular signaling molecules that might modulate these regulatory effects of FGF14. To that end, and building upon our previous investigations suggesting that neuronal Nav channel activity is regulated by a kinase network involving GSK3, AKT, and Wee1, we interrogate in our current investigation how pharmacological inhibition of Wee1 kinase, a serine/threonine and tyrosine kinase that is a crucial component of the G2-M cell cycle checkpoint, affects the Nav1.2 and Nav1.6 channel macromolecular complexes. Our results show that the highly selective inhibitor of Wee1 kinase, called Wee1 inhibitor II, modulates FGF14:Nav1.2 complex assembly, but does not significantly affect FGF14:Nav1.6 complex assembly. These results are functionally recapitulated, as Wee1 inhibitor II entirely alters FGF14-mediated regulation of the Nav1.2 channel, but displays no effects on the Nav1.6 channel. At the molecular level, these effects of Wee1 inhibitor II on FGF14:Nav1.2 complex assembly and FGF14-mediated regulation of Nav1.2-mediated Na+ currents are shown to be dependent upon the presence of Y158 of FGF14, a residue known to be a prominent site for phosphorylation-mediated regulation of the protein. Overall, our data suggest that pharmacological inhibition of Wee1 confers selective modulatory effects on Nav1.2 channel activity, which has important implications for unraveling cellular signaling pathways that fine-tune neuronal excitability. [ABSTRACT FROM AUTHOR]