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Cancer mutations can create neomorphic protein–protein interactions to drive aberrant function1,2. As a substrate receptor of the CULLIN3-RING E3 ubiquitin ligase complex, KBTBD4 is recurrently mutated in medulloblastoma3, the most common embryonal brain tumour in children4. These mutations impart gain-of-function to KBTBD4 to induce aberrant degradation of the transcriptional corepressor CoREST5. However, their mechanism remains unresolved. Here we establish that KBTBD4 mutations promote CoREST degradation through engaging HDAC1/2 as the direct target of the mutant substrate receptor. Using deep mutational scanning, we chart the mutational landscape of the KBTBD4 cancer hotspot, revealing distinct preferences by which insertions and substitutions can promote gain-of-function and the critical residues involved in the hotspot interaction. Cryo-electron microscopy analysis of two distinct KBTBD4 cancer mutants bound to LSD1–HDAC1–CoREST reveals that a KBTBD4 homodimer asymmetrically engages HDAC1 with two KELCH-repeat β-propeller domains. The interface between HDAC1 and one of the KBTBD4 β-propellers is stabilized by the medulloblastoma mutations, which insert a bulky side chain into the HDAC1 active site pocket. Our structural and mutational analyses inform how this hotspot E3–neosubstrate interface can be chemically modulated. First, we unveil a converging shape-complementarity-based mechanism between gain-of-function E3 mutations and a molecular glue degrader, UM171. Second, we demonstrate that HDAC1/2 inhibitors can block the mutant KBTBD4–HDAC1 interface and proliferation of KBTBD4-mutant medulloblastoma cells. Altogether, our work reveals the structural and mechanistic basis of cancer mutation-driven neomorphic protein–protein interactions.

UM171 is a potent agonist of ex vivo human haematopoietic stem cell self-renewal1. By co-opting KBTBD4, a substrate receptor of the CUL3–RING E3 ubiquitin ligase (CRL3) complex, UM171 promotes the degradation of the LSD1–CoREST corepressor complex, thereby limiting haematopoietic stem cell attrition2,3. However, the direct target and mechanism of action of UM171 remain unclear. Here we show that UM171 acts as a molecular glue to induce high-affinity interactions between KBTBD4 and HDAC1/2 to promote corepressor degradation. Through proteomics and chemical inhibitor studies, we identify the principal target of UM171 as HDAC1/2. Cryo-electron microscopy analysis of dimeric KBTBD4 bound to UM171 and the LSD1–HDAC1–CoREST complex identifies an asymmetric assembly in which a single UM171 molecule enables a pair of KELCH-repeat propeller domains to recruit the HDAC1 catalytic domain. One KBTBD4 propeller partially masks the rim of the HDAC1 active site, which is exploited by UM171 to extend the E3–neosubstrate interface. The other propeller cooperatively strengthens HDAC1 binding through a distinct interface. The overall CoREST–HDAC1/2–KBTBD4 interaction is further buttressed by the endogenous cofactor inositol hexakisphosphate, which acts as a second molecular glue. The functional relevance of the quaternary complex interaction surfaces is demonstrated by base editor scanning of KBTBD4and HDAC1. By delineating the direct target of UM171 and its mechanism of action, we reveal how the cooperativity offered by a dimeric CRL3 E3 can be leveraged by a small molecule degrader.

Water column hypoxia is a key process influencing methylmercury (MeHg) production and availability in waterbodies worldwide. During seasonal destratification, large, short-lived pulses of aqueous MeHg may be released into the subsequently mixed water column, but little is known about the fate of these pulses, particularly whether there are concomitant increases in MeHg uptake into aquatic food webs. We examined the magnitude and timing of MeHg uptake across several trophic guilds relative to the reservoir stratification status using biweekly mercury data from water, zooplankton, and fish (Bluegill, Lepomis macrochirusand Smallmouth Bass, Micropterus dolomieu). Zooplankton MeHg concentrations increased by up to 250% during destratification, concurrent with increases in aqueous MeHg concentrations. Zooplankton and filter-passing MeHg concentrations were positively correlated when the reservoir was mixed (R2= 0.95) and destratifying (R2= 0.57) but not while the reservoir was stratified (R2= 0.21). Mercury concentrations in adult bluegill and juveniles of both fish species increased 20–70% following destratification, with responses lagging 4–8 weeks behind those in water and zooplankton MeHg. Mercury concentrations in piscivorous adult bass varied little over the course of the study. Our findings demonstrate the responsiveness of reservoir food webs to pulses in MeHg availability, suggesting that these pulses could play an important role in biotic MeHg exposure within and downstream of reservoirs.

The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor–tezacaftor–deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor–tezacaftor–deutivacaftor compared with standard of care elexacaftor–tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Introduction There is a need for a noninvasive, affordable, sensitive, and specific biomarker to diagnose early acute rejection, to negate the need for frequent biopsies. Dd-cfDNA is a powerful adjunct yet there is limited data on the ethnic differences in its values. There is anecdotal evidence that dd-cfDNA values at rejection may be higher in Black as compared to non-Black recipients. This study aims to add to this literature while defining such variability and comparing it to previously validated cutoffs for dd-cfDNA of 0.5% or 1%.Design This was a single-center retrospective observational study of patients who underwent graft biopsies with a preceding, paired, dd-cfDNA value. Recipients were separated into White, Black, and Hispanic racial and ethnic groups, and dd-cfDNA values at rejection versus nonrejection were compared.Results With 0.5% and 1% cutoffs, false negative rates for rejection were 13% and 22%, respectively. The false positive rate was 38.4%. 12.2% of Black recipients, 11.8% of Hispanic recipients, and 44% of White recipients had rejection with a negative AlloSure®. Values >0.5% corresponded to histologic rejection in 61.5% of Black, 66.7% of White, and 56.3% of Hispanic recipients. Antibody-mediated rejection occurred in 65.5% of rejection cases in Black recipients, while exhibiting the lowest rate of T-cell-mediated rejection. Dd-cfDNA values gave an accurate diagnosis of rejection in 52.8% of recipients with AMR versus 19.3% in TCMR.Conclusion This study demonstrated that dd-cfDNA was applicable to Black recipients with a robust ability to detect antibody-mediated rejection, as compared to White and Hispanic recipients.

General hospitals care for more than 70% of hospitalized children nationally but face challenges in pediatric quality improvement (QI). Feasibility and organizational readiness to change assessments can help inform effective QI. Our objective was to assess readiness to implement pediatric QI interventions among a broad sample of general hospitals participating in the Simultaneously Implementing Pathways for Improving Asthma, Pneumonia, and Bronchiolitis Care for Hospitalized Children (SIP) study.We conducted a mixed-methods study. Data were collected via electronic surveys and qualitative interviews. Participants included multidisciplinary inpatient pediatric clinicians and QI leaders. Surveys used validated tools, including the Organizational Readiness to Implement Change (ORIC) and Feasibility of Intervention Measure (FIM). Interview guides developed using an implementation framework explored feasibility of implementing evidence-based practices. We analyzed data using descriptive statistics and thematic analysis.A total of 424 participants from 15 hospitals were approached, and 186 (44%) completed the survey. ORIC and FIM scores were scaled 1 to 5, with higher scores indicating agreement. Response results did not differ based on clinician type or experience. Clinicians at community hospitals with pediatric beds reported greater readiness than nested children’s hospitals (median ORIC 4.4 vs 4.0, P = 0.02). Interviewees’ (n = 21) anticipated feasibility challenges included aligning practices across hospital care settings and obtaining information technology support for electronic medical record changes.In this mixed-methods study, we found high but variable readiness for pediatric QI and identified specific threats to feasibility. We also illustrated how such assessments can be used to support pediatric QI efforts in general hospitals.

This article presents a direct model predictive control (MPC) scheme for grid-tied converters (GTCs) with LCL filters operating under nominal and adverse grid conditions. Specifically, the proposed MPC algorithm achieves a high-quality grid current in steady state and fast dynamic responses that characterize direct controllers due to the absence of a dedicated modulator. Thanks to the adopted modeling approach, the control and modulation problems are formulated together as a multiple-input multiple-output (MIMO) problem. In doing so, not only the controller design process is greatly simplified, but also favorable performance in terms of controller bandwidth and robustness is achieved. This is in stark contrast to conventional linear control methods, where the existence of different cascaded and/or parallel control loops oftentimes leads to an adverse interaction with each other. Consequently, as also demonstrated by the presented experimental results, the proposed algorithm achieves superior performance for a wide range of operating conditions, rendering it as a promising control approach for the systems in question.

Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein alpha (FAP) are abundant in tumor microenvironments and represent an emerging target for PET cancer imaging. While different quinolone-based small molecule agents have been developed for whole-body imaging, there is a scarcity of well-validated fluorescent small molecule imaging agents to better study these cells in vivo. Here, we report the synthesis and characterization of a series of fluorescent FAP imaging agents based on the common quinolone azide inhibitor. Our data show excellent performance of some synthesized FAP Targeting Fluorescent probes (FTFs) for both topical application and intravenous delivery to label CAF populations in solid tumors. These results suggest that FTF can be used to study CAF biology and therapeutic targeting in vivo.

Driving self-assembly through donor–acceptor interactions to create nanostructured materials is a key feature of supramolecular chemistry; however, the connection between molecular-level changes and larger-scale organization is still unknown. Here, we propose the concept of Lewis adduct binding-induced bond polarization, where the formation of the Lewis adduct leads to a large dipole (here estimated to be 12.5 D), significantly altering the intermolecular interactions between different species and inducing self-assembly. Specifically, a diblock copolymer, poly(2-(dimethylamino)ethyl methacrylate)-polystyrene (PDMAEMA-PS), self-assembles into nanostructured colloidal aggregates on the addition of the Lewis acid tris(pentafluorophenyl) borane (BCF) in toluene. The morphology of the nanostructured colloidal structures is controlled by tuning the block mole fraction of the poly(Lewis base) (polyLB, i.e., PDMAEMA) within the diblock copolymer, resulting in spherical micelles, vesicles, and large compound vesicles with an increasing PDMAEMA block mole fraction. The self-assembly is driven by binding-induced bond polarization during Lewis adduct formation, where the degree of bond polarization of the Lewis adducts is quantified by measuring the dielectric constant of adduct mixtures. We propose that the large dipole formed because of the Lewis adduct leads to substantial changes in the polymer–solvent interactions, driving the self-assembly. The reported findings regarding the Lewis adduct-induced self-assembly in polymer systems have far-ranging potential implications in supermolecular chemistry.

Melanoma is a malignant skin cancer type with a high lethality rate due to active metastasis. Among the risk factors for its development is exposure to ultraviolet radiation (UV) and phenotypical characteristics such as clear skin and eyes. Given the difficulties of the conventional therapy, the high cost of the treatment and the low bioavailability of drugs, it is important to develop new therapeutic methods to circumvent this situation. Nanosystems such as micelles, liposomes and nanoparticles present advantages when compared to conventional treatments. The objective of this paper is to carry out a literature review based on articles that dealt with the use of siRNA-loaded nanosystems for the treatment of melanoma, with trials carried out in vivo to assess tumor size. The search was conducted in the Web of Science and PubMed databases considering the last 5 years, that is, the period between January 2017 to December 2021. The "SiRNA and Drug Delivery Systems and Melanoma" keywords were used in both databases, and the articles were analyzed using the inclusion and exclusion criteria established for this paper. The results obtained indicated that using siRNA transported via nanosystems was capable of silencing the BRAF tumor genes and of reducing tumor size and weight, not presenting in vitro and/or in vivo toxicity. Such being the case, the development of these systems becomes a non-invasive and promising option for the treatment of melanoma.

Introduction: The current gold standard for imaging to rule out extra-hepatic biliary atresia (EHBA) is hepatobiliary scintigraphy (HBS), which involves visually assessing the tracer appearance in the bowel. However, in cases where hepatic function is impaired, biliary-to-bowel transit may not be observable, even in neonatal hepatitis (NH) cases. This study aims to assess the utility of semi-quantitative parameters on HBS to distinguish biliary atresia (BA) from NH when there is a lack of biliary-to-bowel transit for up to 24 h. Materials and methods: The study involved retrospective analysis of patients with the diagnosis of neonatal cholestasis where HBS failed to differentiate BA and NH. Histopathological examination was taken as the gold standard. Semiquantitative parameters calculated include: Liver: blood pool (LBR) and liver: kidney ratios (LKR) at 5 min, 30 min, 1 h and 24 h. Mean values for the two groups were calculated. Student’s t-test was employed to assess the statistical significance of difference of mean between the two groups. Receiver operating characteristic (ROC) curve was also drawn to determine a cut-off of these ratios to differentiate between the two groups using SPSS v26.0. P-value < 0.05 was considered statistically significant. Results: The study included 53 patients (37 males) with a median age of 3 months (range: 24 days to 10 months). Of these, 32 patients had a histopathological diagnosis of BA, while 21 had NH. Mean LBR and LKR at 24 h were statistically different in the two groups (p-value < 0.05). Receiver operating characteristic (ROC) curve analyses showed highest AUC for LBR at 24 h 0.683 (CI:0.532–0.834, p-value 0.017) and LKR at 24 h − 0.669 (CI: 0.511–0.827, p-value:0.036). For diagnosis of BA a cut-off value of ≤4.18 for LBR at 24 h (sensitivity and specificity of 62.5% and 61.9% respectively) and ≤4.64 for LKR at 24 h (sensitivity and specificity of 68.8% and 66.7% respectively) were found to be pertinent. Conclusion: HBS serves as non-invasive imaging of choice to rule out EHBA. Semi-quantitative indices LBR and LKR at the 24-hour can differentiate between EHBA and NH even in cases with compromised hepatic function where traditional visual interpretation of tracer transit proves inadequate.

In November 2007, a black box warning was mandated for rosiglitazone in type 2 diabetes mellitus (T2DM) based on an increased risk of ischemic cardiovascular (CV) events. The Food and Drug Administration (FDA) issued a directive that a CV outcomes trial must be done for any new diabetes drug to demonstrate no CV harm. Therefore, the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial was started in 2011 alongside 13 additional randomized clinical trials (RCTs) of empagliflozin in T2DM. The results of EMPA-REG OUTCOME set the stage for later RCTs in heart failure. Results from these clinical trials have changed the outlook for patients both with and without T2DM and with and without heart failure. A Program Data Monitoring Committee (DMC) with the same core members was utilized for these trials between 2011 and 2024. This committee is likely to be one of the longest serving DMCs since it served 28 trials with empagliflozin between 2011 and 2024. The committee encountered several important challenges which are discussed in this article. Moreover, the committee provides several important take-home messages which we hope will be of value in discussing issues in creating, developing and running DMCs in the future. These include: 1. Whether and when to be blinded and unblinded; 2. How to proceed when the primary endpoint shows no evidence of benefit, but there is evidence for a mortality benefit; 3. Development of presentation of data using figures and boxplots for rapid review of adverse events and laboratory data to assess clinical challenges; 4. How to manage a catastrophic serious adverse event; 5. Suggestions for an ideal structure of the report for the DMC closed session; and 6. The relation between the DMC, sponsor and Contract Research Organization. Our experience emphasizes the value of continuity with the same members serving over a 13-year period.

The article discusses the impact of Donald Trump's presidency on American society, highlighting the erosion of democratic norms and institutions. It criticizes Congress for failing to check executive power and the Democratic Party for losing touch with working-class voters. The labor unions, legal profession, and organized church are also criticized for their lack of action against lawlessness and unethical behavior. The article emphasizes the importance of citizen engagement in upholding democracy and suggests strategies for reclaiming power from corporate interests. [Extracted from the article]

The article discusses the alarming actions taken by President Trump in his early days in office, which are seen as damaging to the country's democratic institutions and the well-being of its citizens. It emphasizes the importance of media coverage of civic groups and unions in resisting these actions and holding the government accountable. The author calls on major newspapers and media outlets to prioritize reporting on these groups to empower their efforts and ensure a more just and democratic society. [Extracted from the article]

The article discusses the author's personal experiences with President Jimmy Carter, highlighting his commitment to engaging with civic groups and advancing consumer protection policies. President Carter appointed numerous progressive leaders to key regulatory agencies and advocated for the creation of a consumer protection agency, despite facing opposition from corporate lobbyists. The article emphasizes Carter's unique approach to prioritizing consumer welfare and contrasts it with subsequent administrations' lack of focus on consumer issues. [Extracted from the article]

Childhood interstitial lung diseases (chILD) are rare and usually severe disorders. Among them, very rare cases of surfactant protein (SP)-B deficiencies have been reported so far and are usually associated with fatal forms of chILD. The RespiRare network allows the collection of precise phenotypic and genotypic information. This study that reports a series of 11 SP-B-deficient patients underscores two key observations: patients with severe loss-of-function variants associated with SP-B complete deficiency presented symptoms at birth and died at a median age of 1 month; and extremely rare cases of hypomorphic variants with partially preserved SP-B function may allow survival.

Anopheles baileyispecies D of the Baileyi Complex, subgenus Anopheles(Diptera: Culicidae) in Thailand is diagnosed and formally named An. inthanonensisSomboon & Harbach, n. sp. Morphological characters of the adults, and the pupal and larval stages with their chaetotaxy, are provided and compared with other species of the complex. Phylogenetic analysis of COIsequences revealed that An. inthanonensisappears to be more closely related to An. monticolain Bhutan and China than it is to other members of the Baileyi Complex.

An extensive mosquito survey was carried out in Hong Kong from September to October 2022, employing a variety of collection methods. Specimens were identified using a combination of morphology and mitochondrial cytochrome C oxidase subunit 1(COI) barcode sequences. Twenty-nine species, including three new records, i.e., Culex bicornutus(Theobald), Culex cinctellusEdwards, and Lutzia chiangmaiensisSomboon & Harbach, were collected. Phylogenetic analysis of COIsequences of Culex annulusTheobald and Culex vishnuiTheobald collected in Hong Kong and elsewhere revealed that the sequences of the two nominal species are genetically very similar and are included in the same clade. Consequently, the synonymy of Cx. annuluswith Cx. vishnuiis reinstated. Lutzia halifaxii(Theobald) is removed from the list of species in Hong Kong and is replaced with Lutzia voraxEdwards, the identification of which is confirmed in the present study. The record of Culex spiculothoraxBram recorded in Hong Kong is replaced with the senior synonym Culex sasaiKano, Nitahara & Awaya. The occurrence of Anopheles fluviatilisJames and Aedes aegypti(Linnaeus) is discussed. Finally, an updated checklist of the mosquitoes of Hong Kong, which now includes 76 species representing 14 genera, is provided, with notation of those species that vector pathogens of human diseases.

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies. The objective response rate was 63.6% (21/33 participants). Median maximal PN volume decrease was 23.6% (range: −48.1% to 5.5%). No disease progression relative to baseline PN volumes occurred before data cutoff, with a median of 28 cycles completed (range: 1–78, 28 d per cycle). Participants experienced decreased tumor pain intensity and pain interference. Adverse events (AEs) were similar to those of the pediatric trial; acneiform rash was the most prevalent AE. Phosphorylation ratios of ERK1/2 decreased significantly (ERK1 median change: −64.6% (range: −99.5% to 90.7%), ERK2 median change: −57.3% (range: −99.9% to 84.4%)) in paired PN biopsies (P≤ 0.001 for both isoforms) without compensatory phosphorylation of AKT1/2/3. The sustained PN volume decreases, associated improvement in pain and manageable AE profile indicate that selumetinib provides benefit to adults with NF1 and inoperable PNs. ClinicalTrials.gov identifier: NCT02407405.

The clinical management of people with multidrug-resistant (MDR) human immunodeficiency virus (HIV) remains challenging despite continued development of antiretroviral agents. A 58-year-old male individual with MDR HIV and Kaposi sarcoma (KS) was treated with a new antiretroviral regimen consisting of anti-CD4 domain 1 antibody UB-421 and capsid inhibitor lenacapavir. The individual experienced delayed but sustained suppression of plasma viremia and a substantial increase in the CD4+T cell count. A longitudinal examination of plasma HIV and infectious isolates showed no evidence of viral evolution or the emergence of UB-421- or lenacapavir-resistant viruses. The individual received three cycles of liposomal doxorubicin and five doses of anti-programmed cell death protein 1 (PD-1) monoclonal antibody pembrolizumab that resulted in improvement in KS with flattening of lesions. Our data demonstrate that combination therapy with UB-421 could provide sustained virologic suppression in people harboring MDR HIV with limited therapeutic alternatives.

Early detection of pancreatic ductal adenocarcinoma (PDAC) can improve survival but is hampered by the absence of early disease symptoms. Imaging remains key for surveillance but is cumbersome and may lack sensitivity to detect small tumors. CA19-9, the only FDA-approved blood biomarker for PDAC, is insufficiently sensitive and specific to be recommended for surveillance. We aimed to discover a blood-based protein signature to improve PDAC detection in our main target population consisting of stage I or II PDAC patients (n= 75) and various controls including healthy controls (n= 50), individuals at high risk (genetic and familial) for PDAC (n= 47), or those under surveillance for an intraductal papillary mucinous neoplasm (n= 36). Roughly 3000 proteins were measured using Olink multiplex technology and conventional immunoassays. Machine learning combined biomarker candidates into 4- to 6-plex signatures. These signatures significantly (p< 0.001) outperformed CA19-9 with 84% sensitivity at 95% specificity, compared to CA19-9’s sensitivity of 53% in the target population. Exploratory analysis was performed in new-onset diabetes (n= 81) and chronic pancreatitis (n= 50) patients. In conclusion, 41 promising biomarker candidates across multiple signatures were identified using proteomics technology and will be further tested in an independent cohort.

The use of prostaglandin infusion to maintain patency of the ductus arteriosus in patients with critical coarctation of the aorta (CoA) to support systemic circulation is the standard of care. However, pulmonary overcirculation resulting from a patent ductus arteriosus in patients with critical CoA is not well described in the literature. We report two cases of critical CoA that required invasive measures to control pulmonary blood flow before surgical repair of the CoA. Both patients had signs of decreased oxygen delivery, hyperlactatemia, and systemic to pulmonary flow via the ductus arteriosus. One patient required surgical pulmonary artery banding and the second patient underwent pulmonary flow restrictor device placement for the control of pulmonary blood flow. A rapid improvement in oxygen delivery and normalization of lactate levels were observed after control of pulmonary overcirculation. Both patients underwent successful surgical repair of the coarctation A and were discharged home.

Strength data can help in guiding the return to sports (RTS) process in patients after an anterior cruciate ligament reconstruction (ACLR). There is need for a fast, cheap, and portable method to monitor muscle strength in patients after ACLR in an ambulatory stetting. Therefore, the purpose of the current study was to assess the use of a hand-held dynamometer (HHD) to monitor hamstring and quadriceps strength after ACLR and to assess the changes over time in patients tested at 3, 6 and 9 months after ACLR. It was hypothesized that patients show greater muscle strength at 6 months after ACLR compared to 3 months, and at 9 months after ACLR compared to 6 months. Forty-four amateur athletes (n = 44) after ACLR participated. Isometric hamstring and quadriceps strength were measured with a HHD at three time points during rehabilitation. Absolute isometric hamstring strength significantly progressed over time. Similar, absolute isometric quadriceps strength significantly progressed over time. This study showed that using handheld dynamometry can be a simple method to monitor the development of absolute isometric hamstring and quadriceps strength in patients after ACLR.

Introduction: Preoperative diagnostic protocols vary worldwide, some prioritizing safety while others question routine procedures. Building on prior research, this study explores the impact of diverse preoperative findings on bariatric management and procedure selection. Methods: In a retrospective analysis of prospective data of over 1000 bariatric surgery patients from January 2017 to December 2022 undergoing primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or sleeve gastrectomy (LSG) were analyzed. Preoperative assessment included upper endoscopy, upper GI series, and esophageal manometry. Sonography data were excluded. The primary endpoint examined the influence of preoperative exams on procedure selection, the secondary endpoint evaluated their therapeutic impact. Results: 897 patients (741 RYGB, 156 SG) were included. All underwent upper endoscopy, revealing common findings such as type C gastritis and reflux esophagitis. Upper endoscopy prompted a therapeutic consequence in 216 patients (24.3%), resulting in a number needed to screen (NNS) of 4.1. Upper GI series and manometry were more frequently performed before LSG. Upper GI series detected hiatal hernias and motility disorders but did not result in any change of procedures. Esophageal manometry found pathologies in 37 (25.3%) patients rising to 41.5% if symptoms were present. Overall, 16 (1.8%) patients experienced a change in the planned procedure, with 14 changes prompted by preoperative findings and two by technical difficulties. Conclusion: We advise routine upper endoscopies for all patients undergoing LRYGB or LSG, while reserving upper GI series only for selected cases. Manometry should be exclusively performed on symptomatic patients undergoing LSG, ensuring a balanced and individualized preoperative assessment. Graphical abstract:

To describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRXgene (CRX-RDs).

Study Design Retrospective bicentric Cohort Study.Objective Posterior (PLIF) and transforaminal lumbar interbody fusion (TLIF) have been clinically proven for the surgical treatment of degenerative spinal disorders. Despite many retrospective studies, the superiority of either technique has not been proven to date. In the literature, the complication rate of the conventional PLIF technique is reported to be significantly higher, but with inconsistent complication recording. In this retrospective bicentric study, a less invasive PLIF technique was compared with the conventional TLIF technique and complications were recorded using the validated SAVES V2 classification system.Methods 1142 patients underwent PLIF (702) or TLIF (n = 440) up to 3 levels in two specialized centers. Epidemiological data, intra- and postoperative complications during hospitalization and after discharge were analyzed according to SAVES V2.Results The overall complication rate was 13.74%. TLIF-patients had slightly significant more complications than PLIF-patients (TLIF = 16.6%/PLIF = 11.9%, P= .0338). Accordingly, complications during revision surgeries were more frequent in the first cohort (TLIF = 20.9%/PLIF = 12.6%; P= .03252). In primary interventions, the surgical technique did not correlate with the complication rate (TLIF = 12.4%/PLIF = 11.7%). There were no significant differences regarding severity of complications.Conclusions An important component of this work is the complication recording according to a uniform classification system (SAVES V2). In contrast to previous literature, we could demonstrate that there is not a significant difference between the two surgical techniques.