RAB1A haploinsufficiency phenocopies the 2p14-p15 microdeletion and is associated with impaired neuronal differentiation.

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C>T [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and a mosaic missense mutation (c.83T>C [p.Leu28Pro]), were identified in three individuals with similar neurodevelopmental presentations. In rescue experiments, production of the full-length, but not the truncated, RAB1a rescued Golgi structure and cell proliferation in Rab1-depleted cells. In contrast, the missense-variant RAB1a disrupted Golgi structure despite intact Rab1 expression, suggesting a dominant-negative function of the mosaic missense mutation. Knock-down of RAB1A in cultured human embryonic stem cell-derived neurons resulted in impaired neuronal arborization. Finally, RAB1A is located within the 2p14-p15 microdeletion syndrome locus. The similar clinical presentations of individuals with RAB1A loss-of-function mutations and the 2p14-p15 microdeletion syndrome implicate loss of RAB1A in the pathogenesis of neurodevelopmental manifestations of this microdeletion syndrome. Our study identifies a RAB1A-related neurocognitive disorder with speech and motor delay, demonstrates an essential role for RAB1a in neuronal differentiation, and implicates RAB1A in the etiology of the neurodevelopmental sequelae associated with the 2p14-p15 microdeletion syndrome.

Epigenetic activation of SOX11 is associated with recurrence and progression of ductal carcinoma in situ to invasive breast cancer.

BACKGROUND: Risk of recurrence and progression of ductal carcinoma in situ (DCIS) to invasive cancer remains uncertain, emphasizing the need for developing predictive biomarkers of aggressive DCIS. METHODS: Human cell lines and mouse models of disease progression were analyzed for candidate risk predictive biomarkers identified and validated in two independent DCIS cohorts. RESULTS: RNA profiling of normal mammary and DCIS tissues (n = 48) revealed that elevated SOX11 expression correlates with MKI67, EZH2, and DCIS recurrence score. The 21T human cell line model of DCIS progression to invasive cancer and two mouse models developing mammary intraepithelial neoplasia confirmed the findings. AKT activation correlated with chromatin accessibility and EZH2 enrichment upregulating SOX11 expression. AKT and HER2 inhibitors decreased SOX11 expression along with diminished mammosphere formation. SOX11 was upregulated in HER2+ and basal-like subtypes (P < 0.001). Longitudinal DCIS cohort (n = 194) revealed shorter recurrence-free survival in SOX11+ than SOX11- patients (P = 0.0056 in all DCIS; P < 0.0001 in HER2+ subtype) associated with increased risk of ipsilateral breast event/IBE (HR = 1.9, 95%CI = 1.2-2.9; P = 0.003). DISCUSSION: Epigenetic activation of SOX11 drives recurrence of DCIS and progression to invasive cancer, suggesting SOX11 as a predictive biomarker of IBE.

Live-cell fluorescence imaging of microgametogenesis in the human malaria parasite Plasmodium falciparum.

Formation of gametes in the malaria parasite occurs in the midgut of the mosquito and is critical to onward parasite transmission. Transformation of the male gametocyte into microgametes, called microgametogenesis, is an explosive cellular event and one of the fastest eukaryotic DNA replication events known. The transformation of one microgametocyte into eight flagellated microgametes requires reorganisation of the parasite cytoskeleton, replication of the 22.9 Mb genome, axoneme formation and host erythrocyte egress, all of which occur simultaneously in <20 minutes. Whilst high-resolution imaging has been a powerful tool for defining stages of microgametogenesis, it has largely been limited to fixed parasite samples, given the speed of the process and parasite photosensitivity. Here, we have developed a live-cell fluorescence imaging workflow that captures the entirety of microgametogenesis. Using the most virulent human malaria parasite, Plasmodium falciparum, our live-cell approach captured early microgametogenesis with three-dimensional imaging through time (4D imaging) and microgamete release with two-dimensional (2D) fluorescence microscopy. To minimise the phototoxic impact to parasites, acquisition was alternated between 4D fluorescence, brightfield and 2D fluorescence microscopy. Combining live-cell dyes specific for DNA, tubulin and the host erythrocyte membrane, 4D and 2D imaging together enables definition of the positioning of newly replicated and segregated DNA. This combined approach also shows the microtubular cytoskeleton, location of newly formed basal bodies, elongation of axonemes and morphological changes to the erythrocyte membrane, the latter including potential echinocytosis of the erythrocyte membrane prior to microgamete egress. Extending the utility of this approach, the phenotypic effects of known transmission-blocking inhibitors on microgametogenesis were confirmed. Additionally, the effects of bortezomib, an untested proteasomal inhibitor, revealed a clear block of DNA replication, full axoneme nucleation and elongation. Thus, as well as defining a framework for broadly investigating microgametogenesis, these data demonstrate the utility of using live imaging to validate potential targets for transmission-blocking antimalarial drug development.

Cryoballoon pulmonary vein isolation versus radiofrequency ablation of the pulmonary veins and left atrial posterior wall: Patient-reported outcomes.

BACKGROUND: Data are lacking on patient-reported outcomes (PRO) following cryoballoon ablation (CBA) versus radiofrequency ablation (RFA). We sought to evaluate QoL and clinical outcomes of cryoballoon pulmonary vein isolation only (CRYO-PVI-ONLY) versus RFA with PVI and posterior wall isolation (RF-PVI+PWI) in a large prospective PRO registry. METHODS: Patients who underwent AF ablation (2013-2016) at our institution were enrolled in an automated, prospectively maintained PRO registry. CRYO-PVI-ONLY patients were matched (1:1) with RF-PVI+PWI patients based on age, gender, and type of AF (paroxysmal vs. persistent). QoL and clinical outcomes were assessed using PRO surveys at baseline and at 1-year. The atrial fibrillation symptom severity scale (AFSSS) was the measure for QoL. Additionally, we assessed patient-reported clinical improvement, arrhythmia recurrence, and AF burden (as indicated by AF frequency and duration scores). RESULTS: A total of 296 patients were included (148 in each group, 72% paroxysmal). By PRO, a significant improvement in QoL was observed in the overall study population and was comparable between CRYO-PVI-ONLY and RF-PVI+PWI (baseline median AFSSS of 11.5 and 11; reduced to 2 and 4 at 1 year, respectively; p = 0.44). Similarly, the proportion of patients who reported improvement in their overall QoL and AF related symptoms was high and similar between the study groups [92% (CRYO-PVI-ONLY) vs. 92.8% (RF-PVI+PWI); p = 0.88]. Arrhythmia recurrence was significantly more common in the CRYO-PVI-ONLY group (39.7%) compared to RF-PVI+PWI (27.7 %); p = 0.03. Comparable results were observed in paroxysmal and persistent AF. CONCLUSION: CRYO-PVI-ONLY and RF-PVI+PWI resulted in comparable improvements in patient reported outcomes including QoL and AF burden; with RF-PVI+PWI being more effective at reducing recurrences.

The SAGES MASTERS program bariatric surgery pathway selects 10 seminal publications on revisional bariatrics.

BACKGROUND: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program designated bariatric surgery as a clinical pathway. Among the tiers of the Masters Program, revisional bariatric surgery is the highest tier of "mastery" within the pathway. This article presents the top 10 seminal studies representing the current landscape of revisional bariatrics. METHODS: The literature was systematically searched and seminal articles designated by consensus agreement of the SAGES Metabolic and Bariatric Surgery committee using multiple criteria, including impact on the field, citation frequency, and expert opinion. Articles were reviewed by committee members and presented in summarized fashion. RESULTS: The top 10 papers are presented in grouped thematic categories covering the early evolution of revisional bariatrics, changing criteria for reoperative bariatric surgery, divergence of revision versus conversion bariatric surgery, and recent technologic innovations in revisional bariatric surgery. Each summary is presented with expert appraisal and commentary. CONCLUSION: These seminal papers represent a snapshot of the dynamic field of revisional bariatric surgery and emphasize the need to not only remain current with contemporary trends but also keep a patient-oriented perspective on patient and intervention selection for optimal success.

Effect of intraoral administration of parathyroid hormone on osseous and soft tissue healing around implants in ovariectomized rat maxillae.

OBJECTIVES: Intermittent administration of parathyroid hormone (PTH) increases systemic bone mass. However, the effect of PTH on osseous and soft tissue healing around implants in osteoporosis patients remains unclear. This study aimed to investigate the effects of PTH on tissue healing around implants in ovariectomized rats and to compare systemic and intraoral administration routes. MATERIAL AND METHODS: Implants were placed at the healed sites of ovariectomized rats 3 weeks after maxillary first molar extraction. Rats were randomly divided into two groups that received either daily systemic subcutaneous or local intraoral PTH administration. Maxillae were dissected to examine bone architectures with micro-computed tomography images. Histomorphometric and immunohistochemical analyses were performed to evaluate osseous and soft tissue healing around the implants. RESULTS: Regardless of the administration route, PTH significantly increased bone area and the numbers of osteoblasts, osteoclasts, and osteocytes in the first and second inside and outside areas of implant threads, in addition to decreasing the number of sclerostin+ osteocytes. However, the intraoral PTH administration route was superior to the systemic route by significantly improving bone quality and promoting collagen production in the connective tissue around implants. CONCLUSIONS: Parathyroid hormone administration promoted both osseous and soft tissue healing around implants, irrespective of administration route. Interestingly, intraoral administration improved the evaluated parameters more than systemic administration. Thus, the intraoral route could become a useful treatment strategy for implant treatment in osteoporosis patients.

Association Between Tranexamic Acid and Decreased Periprosthetic Joint Infection Risk in Patients Undergoing Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Over 2 Million Patients.

BACKGROUND: The purpose of this study was to perform a systematic review and meta-analysis to evaluate the association between tranexamic acid (TXA) use during primary total hip arthroplasty (THA) and primary total knee arthroplasty (TKA), and the risk of developing periprosthetic joint infection (PJI) after these procedures. METHODS: A systematic review was carried out from inception to October 17, 2022. There were 6 studies that were ultimately included in the meta-analysis. The association between the development of PJI and TXA was analyzed using odds ratios (ORs) with 95% confidence intervals (CIs) and estimates of risk difference (RD). Subgroup analysis was performed to evaluate only studies reporting out to 90 days of follow-up versus more than 90 days of follow-up. RESULTS: Among 2,098,469 arthroplasties, TXA utilization was associated with an overall lower risk of PJI (OR = 0.63 [95% CI 0.42 to 0.96], P < .001) and a 0.4% lower incidence of PJI (RD = -0.0038, 95% CI [-0.005 to -0.002], P < .001). When subgrouping the studies according to length of follow-up, TXA was associated with a lower risk of PJI (OR = 0.43 [95% CI 0.35 to 0.53], P < .001) and a 1% lower incidence of PJI (RD = -0.0095 [95% CI -0.013 to -0.005], P < .001) in patients followed for more than 90 days. CONCLUSIONS: This meta-analysis demonstrates that TXA use is associated with a reduced risk of PJI, with our RD analysis identifying an approximately 0.4% reduction in PJI rates with TXA use. These findings provide even more data to support the routine use of TXA during primary THA and primary TKA.

Barriers to a successful healthcare transition for individuals with urea cycle disorders.

The pediatric to adult healthcare transition (HCT) is a process for individuals with chronic health conditions to gradually shift from a pediatric to an adult-oriented care system. Autonomy and self-management skills required for an individual's HCT readiness can be evaluated through the transition readiness assessment questionnaire (TRAQ). Despite general HCT preparation guidelines, little is known about the HCT experience of individuals with a urea cycle disorder (UCD). This is the first study to report the parent or guardian perception of the HCT process in children with a UCD by investigating the stages of transition readiness and transition outcome. We identify barriers to HCT readiness and planning, along with deficiencies in transition outcome for individuals with a UCD. For children that received special education services compared to those that did not, significantly lower transition readiness scores were identified in the total TRAQ score (p = 0.03) and in the domains of tracking health issues (p = 0.02), talking with providers (p = 0.03), and managing daily activities (p = 0.01). There was a lack of HCT preparation as most subjects did not have a HCT discussion with their healthcare provider before age 26. Deficiencies in HCT outcome are demonstrated by individuals with a UCD reporting delays in needed medical care and dissatisfaction with their healthcare services. Considerations for facilitating a successful HCT for individuals with a UCD include providing individualized education, appointing a transition coordinator, allowing flexibility in HCT timing, and ensuring that the individual recognizes concerning UCD symptoms and knows when to seek medical care.

Age-Stratified 30-day Rehospitalization and Mortality and Predictors of Rehospitalization Among Patients With Systemic Lupus Erythematosus: A Medicare Cohort Study.

OBJECTIVE: Recent studies suggest young adults with systemic lupus erythematosus (SLE) have high 30-day readmission rates, which may necessitate tailored readmission reduction strategies. To aid in risk stratification for future strategies, we measured 30-day rehospitalization and mortality rates among Medicare beneficiaries with SLE and determined rehospitalization predictors by age. METHODS: In a 2014 20% national Medicare sample of hospitalizations, rehospitalization risk and mortality within 30 days of discharge were calculated for young (aged 18-35 yrs), middle-aged (aged 36-64 yrs), and older (aged 65+ yrs) beneficiaries with and without SLE. Multivariable generalized estimating equation models were used to predict rehospitalization rates among patients with SLE by age group using patient, hospital, and geographic factors. RESULTS: Among 1.39 million Medicare hospitalizations, 10,868 involved beneficiaries with SLE. Hospitalized young adult beneficiaries with SLE were more racially diverse, were living in more disadvantaged areas, and had more comorbidities than older beneficiaries with SLE and those without SLE. Thirty-day rehospitalization was 36% among young adult beneficiaries with SLE-40% higher than peers without SLE and 85% higher than older beneficiaries with SLE. Longer length of stay and higher comorbidity risk score increased odds of rehospitalization in all age groups, whereas specific comorbid condition predictors and their effect varied. Our models, which incorporated neighborhood-level socioeconomic disadvantage, had moderate-to-good predictive value (C statistics 0.67-0.77), outperforming administrative data models lacking comprehensive social determinants in other conditions. CONCLUSION: Young adults with SLE on Medicare had very high 30-day rehospitalization at 36%. Considering socioeconomic disadvantage and comorbidities provided good prediction of rehospitalization risk, particularly in young adults. Young beneficiaries with SLE with comorbidities should be a focus of programs aimed at reducing rehospitalizations.

The efficacy and safety of subcutaneous continuous local infiltration analgesia with ropivacaine in patients undergoing total knee arthroplasty: a comparative study.

BACKGROUND: Continuous local infiltration analgesia (CLIA) can be administered via intraarticular or periarticular techniques in patients undergoing total knee arthroplasty (TKA). The purpose of this investigation was to retrospectively report a single-center experience of epidural analgesia with subcutaneous CLIA versus epidural analgesia without CLIA among patients undergoing TKA. METHODS: This single-center retrospective study was conducted in Saudi Arabia. From January 01, 2014, to December 30, 2020, medical records of all patients who underwent TKA were reviewed. Patients who received subcutaneous CLIA with epidural analgesia were assigned to the intervention group, whereas those who received epidural analgesia without subcutaneous CLIA were assigned to the control group. The efficacy endpoints included: (i) postoperative pain scores at 24 h, 48 h, 72 h, and 3 months; (ii) postoperative opioid consumption at 24 h, 48 h, 72 h, and 24-72 h (cumulative); (iii) length of hospital stay; and (iv) postoperative functional recovery of the knee 3 months post-operation, according to the Knee Injury and Osteoarthritis Outcome Score. RESULTS: At rest and during mobilization, the CLIA group (n = 28) achieved significantly lower postoperative pain scores 24 h, 48 h, 72 h, and 3 months post-operation than the non-CLIA group (n = 35). Subgroup analysis revealed that the CLIA group achieved significantly less opioid consumption 24 h and 48 h post-operation than the non-CLIA group. There was no difference between the groups regarding the length of hospital stay or functional scores 3 months post-operation. There was no significant difference between the groups regarding the rate of wound infection, other infections, and readmission within 30 days. CONCLUSION: Subcutaneous CLIA is a technically feasible and safe procedure without major adverse events but with reduced postoperative pain scores (at rest and during mobilization) and opioid consumption. Additional larger studies are warranted to confirm our results. Moreover, a head-to-head comparison between subcutaneous CLIA and periarticular or intraarticular CLIA is an interesting prospective investigation.

COVID-19 dynamics and immune response: Linking within-host and between-host dynamics.

The global impact of COVID-19 has led to the development of numerous mathematical models to understand and control the pandemic. However, these models have not fully captured how the disease's dynamics are influenced by both within-host and between-host factors. To address this, a new mathematical model is proposed that links these dynamics and incorporates immune response. The model is compartmentalized with a fractional derivative in the sense of Caputo-Fabrizio, and its properties are studied to show a unique solution. Parameter estimation is carried out by fitting real-life data, and sensitivity analysis is conducted using various methods. The model is then numerically implemented to demonstrate how the dynamics within infected hosts drive human-to-human transmission, and various intervention strategies are compared based on the percentage of averted deaths. The simulations suggest that a combination of medication to boost the immune system, prevent infected cells from producing the virus, and adherence to COVID-19 protocols is necessary to control the spread of the virus since no single intervention strategy is sufficient.

CBCT Analysis of Oropharynx Airway Volume.

OBJECTIVE: The study was performed to analyze the oropharynx airway and examine the influence of age and gender on the oropharynx volume configuration using cone beam computed tomography. MATERIALS AND METHODS: This study examined the cone beam computed tomographic images of 51 patients 25 male and 26 females, group matched for age and gender. The oropharynx airway volume and area between the posterior nasal spine and top of the epiglottis were measured and compared. RESULTS: The statistical measurements of 51 cone beam computed tomography images showed a nonsignificant difference found between male and female regarding the age (the mean age for female 40.15 y. and for male32.72 y). Male subjects had greater oropharynx volume, a high significant difference ( P =0.005) in oropharynx volume between the 3 age groups. A significant difference was found between the smallest age group with the larger age groups. CONCLUSION: The study data revealed that the changes in measurements of oropharynx airway are age-dependent in addition to gender effect.

Synchronised Video-assisted Clinical Skill Lab Sessions (SVCSLSs). Can SVCSLSs fill some gaps in virtual medical education? A mixed-method study.

Despite the recent advancement of virtual education during the last pandemic, mastering clinical competencies remains challenging. The current study endorsed Synchronised Video-assisted Clinical Skill lab Sessions (SVCSLS) as a novel instructional design aiming to improve medical students' clinical competencies during virtual learning. The current study is a mixed-method study that was carried out among 210 medical students at a medical college in Saudi Arabia. It was revealed that students viewed SVCSLSs as an effective and safe tool during times of crisis. Students' performance did not show significant variations in all program phases compared with face-to-face learning. SVCSLSs has many advantages, including enjoyment, continuous access to learning material, Self-Directed Learning, fostering recall and memorisation, and enhancing higher cognitive skills. Students suggested that the sessions' content be updated, that workplace-related videos be added, and that constructive feedback is provided. Students recommended updating the contents of the sessions, enriching them with workplace-based videos, and providing constructive feedback. Though SVCSLSs have been proven to be an effective tool, we recommend using them during a crisis rather than replacing the face-to-face mode of learning in normal circumstances.

Medication-related osteonecrosis of the jaw: A literature review and update.

Since the initial description of medication-related osteonecrosis of the jaw (MRONJ) almost two decades ago, the potential pathophysiology and risk factors have been elaborated on in many investigations and guidelines. However, the definitive pathophysiology based on scientific evidence remains lacking. Consequently, the optimal clinical treatment and prevention strategies for MRONJ have not been established. Despite their different mechanisms of action, many drugs, including bisphosphonates, denosumab, angiogenesis inhibitors, and other medications, have been reported to be associated with MRONJ lesions in cancer and osteoporosis patients. Importantly, MRONJ occurs predominantly in the jawbones and other craniofacial regions, but not in the appendicular skeleton. In this up-to-date review, the currently available information and theories regarding MRONJ are presented from both clinical and basic science perspectives. The definition and epidemiology of MRONJ, triggering medication, and histopathology are comprehensively summarized. The immunopathology and the potential pathophysiology based on immune cells such as neutrophils, T and B cells, macrophages, dendritic cells, and natural killer cells are also discussed. In addition, antiangiogenesis, soft tissue toxicity, necrotic bone, osteocyte death, and single-nucleotide polymorphisms are examined. Moreover, other possible mechanisms of MRONJ development are considered based on the unique embryological characteristics, different cell behaviors between jawbones and appendicular skeleton, unique anatomical structures, and sustained bacterial exposure in the oral cavity as a basis for MRONJ site specificity. Based on the literature review, it was concluded that multiple factors may contribute to the development of MRONJ, although which one is the key player triggering MRONJ in the craniofacial region remains unknown.

Perinatal factors, female breast cancer, and associated risk factors in Puerto Rico: evidence from the Atabey epidemiology of breast cancer study.

PURPOSE: There is increasing evidence that exposures in utero and in infancy impact breast cancer risk. No previous studies have evaluated these associations among women in Puerto Rico. METHODS: In a population-based case-control study of breast cancer epidemiology in the San Juan metropolitan area in Puerto Rico, we examined the association of early life factors with breast cancer risk and breast cancer risk factors. Both cases (n = 315) and controls (n = 348) completed interviewer-administered questionnaires, including self-reported birth country, birthweight, and history of having been breastfed. Comparisons of characteristics of those with and without the early life factors were made with t-tests or chi-squared tests; associations between early life factors and breast cancer risk were estimated with unconditional logistic regression adjusting for age, education, body mass index (BMI), age at menarche, parity, and menopausal status. RESULTS: Women who had been breastfed tended to have higher adult body mass index (BMI), higher education, and lower parity (p < 0.05). Higher birthweight was associated with higher adult BMI and lower educational attainment (p < 0.05). Those born outside of Puerto Rico or the US were more likely to have higher educational attainment and earlier age at menarche than those born within Puerto Rico or the US (p < 0.05). We found no significant associations between any of the early life factors and breast cancer risk. CONCLUSION: We did not find evidence of an association of early life factors with breast cancer risk among women in Puerto Rico.

Genetic care in geographically isolated small island communities: 8 years of experience in the Dutch Caribbean.

Worldwide, there are large inequalities in genetic service delivery. In 2011, we established a bi-annual joint pediatric-genetics clinic with a visiting clinical geneticist in the Dutch Caribbean. This retrospective study evaluates the yield of diagnostic testing and the clinical utility of a diagnosis for patients with rare diseases on these relatively isolated, resource-limited islands. A total of 331 patients that were referred to the clinical geneticist between November 2011 and November 2019 and had genetic testing were included in this study. A total of 508 genetic tests were performed on these patients. Microarray, next-generation sequencing gene panels, and single-gene analyses were the most frequently performed genetic tests. A molecularly confirmed diagnosis was established in 33% of patients (n = 108). Most diagnosed patients had single nucleotide variants or small insertions and/or deletions (48%) or copy number variants (34%). Molecular diagnostic yield was highest in patients referred for seizures and developmental delay/intellectual disability. The genetic diagnosis had an impact on clinical management in 52% of patients. Referrals to other health professionals and changes in therapy were the most frequently reported clinical consequences. In conclusion, despite limited financial resources, our genetics service resulted in a reasonably high molecular diagnostic yield. Even in this resource-limited setting, a genetic diagnosis had an impact on clinical management for the majority of patients. Our approach with a visiting clinical geneticist may be an example for others who are developing genetic services in similar settings.

The SAGES MASTERS program presents the 10 seminal articles for Roux-en-Y gastric bypass.

BACKGROUND: One of the eight clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program is bariatric surgery which includes three anchoring procedures. For each anchoring procedure sentinel articles have been identified to enhance participant surgeon lifelong learning. Roux-en-Y gastric bypass (RYGB) is one of the 3 anchoring procedures for the Bariatric Pathway. In this article we present the top 10 seminal articles regarding the RYGB which surgeons should be familiar with. METHODS: The literature was systematically searched to identify the most cited papers on RYGB. The SAGES Metabolic and Bariatric Surgery committee reviewed the most cited article list and using expert consensus selected the seminal articles that every bariatric surgeon should read. These articles were reviewed in detail by committee members and are presented here. RESULTS: The top 10 most cited sentinel papers on RYGB focus on operative safety, outcomes, surgical technique, and physiologic changes after the procedure. A summary of each paper is presented here, including expert appraisal and commentary. CONCLUSION: The seminal articles presented here have supported the widespread acceptance and use of the RYGB by bolstering the understanding of its mechanism of action and by demonstrating its safety and excellent patient outcomes. All bariatric surgeons should be familiar with these 10 landmark articles.

A Commentary on the "Duration of Oral Antibiotics Administration for Cetuximab-Induced Acneiform Eruption".

Acneiform eruption is a devastating cutaneous side effect of cetuximab, a monoclonal antibody used to treat a variety of cancers. Despite its effectiveness, many patients avoid or discontinue it after experiencing its dermatological side effects as it negatively impacts their quality of life (QoL). This displays the immense need for multidisciplinary collaboration to prevent and treat cetuximab-induced acneiform eruption (CIAE). Prevention methods include, but are not limited to, education, skin care routines, and prophylactic drugs. The following measures reduce the likelihood of developing CIAE and decrease its severity, making it easier to treat if it were to occur. Ongoing research on the treatment of CIAE continues. Of these treatments, oral tetracyclines and systemic corticosteroids have been shown to be the most effective by far. This commentary aims to evaluate the study by Park et al. [Dermatology. 2021;237(3):457-63], further elaborate on prevention and treatment measures of CIAE, and highlight the implications of CIAE on a patient's QoL.

Oral health-related quality of life in children with celiac disease.

PURPOSE: There is limited knowledge about oral health-related quality of life (OHRQoL) in children with celiac disease (CD). This study aimed to assess OHRQoL in children with CD compared to healthy controls. METHODS: This case-control study included children with CD and healthy controls. Three scales were used to assess OHRQoL in different age groups: 6-7 years, 8-10 years, and 11-14 years. The OHRQoL scores were compared between cases and controls to examine the possible associations between OHRQoL and demographics, socioeconomic status, and oral health. RESULTS: Overall, 104 children with CD and 104 healthy children (controls) were included. The mean age was 10.67 ± 2.39 years in CD patients and 10.69 ± 2.36 in controls (P = 0.971). Male and female children constituted 50% of each group. Children with CD had significantly higher OHRQoL scores than controls (P = 0.003). Low education levels of parents of children with CD and a higher number of siblings in controls were associated with high OHRQoL scores (P = 0.002, P < 0.020, and P = 0.010, respectively). Recurrent aphthous stomatitis (RAS) increased the OHRQoL scores by 7.5 on average (P = 0.016). CONCLUSION: Children with CD had poor OHRQoL compared with healthy controls. Poor OHRQoL in children with CD was associated with RAS and with lower parental income and education. RAS was an independent predictor of poor OHRQoL in children with CD.

The first modified Delphi consensus statement on sleeve gastrectomy.

INTRODUCTION: Sleeve gastrectomy (SG) is the commonest bariatric procedure worldwide. Yet there is significant variation in practice concerning its various aspects. This paper report results from the first modified Delphi consensus-building exercise on SG. METHODS: We established a committee of 54 globally recognized opinion makers in this field. The committee agreed to vote on several statements concerning SG. An agreement or disagreement amongst ≥ 70.0% experts was construed as a consensus. RESULTS: The committee achieved a consensus of agreement (n = 71) or disagreement (n = 7) for 78 out of 97 proposed statements after two rounds of voting. The committee agreed with 96.3% consensus that the characterization of SG as a purely restrictive procedure was inaccurate and there was 88.7% consensus that SG was not a suitable standalone, primary, surgical weight loss option for patients with Barrett's esophagus (BE) without dysplasia. There was an overwhelming consensus of 92.5% that the sleeve should be fashioned over an orogastric tube of 36-40 Fr and a 90.7% consensus that surgeons should stay at least 1 cm away from the angle of His. Remarkably, the committee agreed with 81.1% consensus that SG patients should undergo a screening endoscopy every 5 years after surgery to screen for BE. CONCLUSION: A multinational team of experts achieved consensus on several aspects of SG. The findings of this exercise should help improve the outcomes of SG, the commonest bariatric procedure worldwide, and guide future research on this topic.