Comparing Safety and Efficacy Outcomes of Gastric Bypass and Sleeve Gastrectomy in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Sleeve Gastrectomy (SG) could be done by the removal of a big portion of the stomach, leading to reduced amounts of food taken as a result of the smaller stomach size. In contrast, Roux-en-Y Gastric Bypass (RYGB) can be done by creating a small stomach pouch and rerouting a part of the small intestine, employing combined mechanisms of restriction and malabsorption to limit food intake and modify nutrient absorption. Our aim is to identify the most effective and safest surgical intervention for individuals with both Type 2 Diabetes Mellitus (T2DM) and obesity, considering both short and long-term outcomes. We will assess participants undergoing either SG or RYGB to determine the optimal surgical approach. We made a thorough search of PubMed, Cochrane Library, Scopus, and Web of Science databases up to November 2023. Our focus was on randomized controlled trials (RCTs) comparing the safety and efficacy of RYGB and SG in T2DM regarding any extractable data. We excluded studies of other designs, such as cohorts, case reports, case series, reviews, in vitro studies, postmortem analyses, and conference abstracts. Utilizing Review Manager 5.4, we performed a meta-analysis, combining risk ratios (RR) with a 95% confidence interval (CI) conducted for binary outcomes, while mean with SD and 95% CI are pooled for the continuous ones. The total number of participants in our study is 4,148 patients. Our analysis indicates superior outcomes in the group undergoing RYGB surgery compared to the SG group (RR = 0.76, 95% (CI) (0.66 to 0.88), P = 0.0002). The pooled data exhibited homogeneity (P = 0.51, I2 = 0%) after employing the leave-one-out method. For the 1-3 year period, six studies involving 332 patients with T2DM yielded non-significant results (RR = 0.83, 95% CI (0.66 to 1.06), P = 0.14) with homogeneity (P = 0.24, I2 = 28%). Conversely, the 5-10 year period, with six studies comprising 728 DM patients, demonstrated significant results (RR = 0.69, 95% CI (0.56 to 0.85), P = 0.14) and homogeneity (P = 0.84, I2 = 0%). In terms of total body weight loss, our findings indicate significantly higher weight loss with RYGB (mean difference (MD) = -6.13, 95% CI (-8.65 to -3.6), P > 0.00001). However, pooled data exhibited considerable heterogeneity (P > 0.00001, I2 = 93%). Subgroup analyses for the 1-3 year period (five studies, 364 DM patients) and 5-10 year period (six studies, 985 DM patients) also revealed significant differences favoring RYGB, with heterogeneity observed in both periods (1-3 years: P > 0.00001, I2 = 95%; 5-10 years: P = 0.001, I2 = 75%). RYGB demonstrated significant long-term improvement in diabetes remission and superior total body weight loss compared to SG. While no notable differences were observed in other efficacy outcomes, safety parameters require further investigation. no significant distinctions were found in any of the safety outcomes: hypertension (HTN), high-density lipoprotein (HDL), hyperlipidemia, fasting blood glucose, vomiting, low-density lipoprotein (LDL), and total cholesterol. Further research is essential to comprehensively assess safety outcomes for both surgical approaches.

Show don't tell: assessing the impact of co-developed patient information videos in paediatric uveitis.

BACKGROUND/OBJECTIVES: There is a paucity of online educational content targeting children and young people with uveitis. We evaluated the impact of a co-designed patient education video on subjective and objective understanding of childhood uveitis. SUBJECTS/METHODS: Co-designed patient education media were produced in collaboration with the Childhood Uveitis Studies steering group and the Great Ormond Street Hospital Generation R Young People's Advisory Group and narrated by children. Patients managed within the Uveitis service at GOSH were invited to take part in a pre-post survey, undertaken immediately prior to and following viewing of a patient education video. RESULTS: Forty-three patients participated. These were stratified according to age, duration of disease, and treatment type for analysis. Self-rated knowledge improved across all groups (p = 0.001), particularly in those with a new diagnosis of uveitis (Z = -8.124, p < 0.001). Objective knowledge scores improved across all questions, especially in younger children, those with new disease, and those on steroid only treatment (Z = -3.847, p < 0.001, Z = -3.975, p < 0.001, Z = -3.448, p < 0.001; respectively). Most participants reported the videos to be easy to understand and with the right amount of information. All stated that they learned something new. CONCLUSIONS: Patient understanding of disease and treatment is crucial to achieving the best possible outcomes for this chronic, relapsing remitting and potentially blinding disorder. Our findings data shows the potential value of co-designed patient information videos, specifically in our study benefitting younger patients and those recently diagnosed. We suggest that other clinical teams could collaborate fruitfully with patient groups to develop similar videos to target possible misinformation and potentially improve patient outcomes.

Potential significance of podoplanin immunohistochemical expression in papillary thyroid carcinoma.

Podoplanin (PDPN) is a lymphatic endothelial marker expressed by a range of human malignancies in which it has been shown to contribute to tumor progression and metastasis. However, there is a lack of the studies, examining the function of PDPN in thyroid cancer. The current study was performed to explore the possible diagnostic value of PDPN expression in papillary thyroid cancer (PTC) and to evaluate the marker's potential for prediction of regional lymph node metastasis. Lymphatic vascular density (LVD) and the stromal/cancer-associated fibroblasts (CAFs), labeled by PDPN, were examined in PTC compared to the other thyroid lesions. The current study included 50 cases of PTC and 50 cases of non-PTC thyroid lesions. Immunohistochemical staining was performed using monoclonal PDPN antibodies. Podoplanin expression was scored as positive and negative. Podoplanin expression was found in 36% of PTC cases, but it was not found in benign, low risk (borderline), or malignant lesions other than PTC. Furthermore, lymph node metastasis was significantly correlated with PDPN expression, LVD and CAFs (p-values < 0.00001, < 0.001 and 0.0002 respectively). These findings support the diagnostic utility of PDPN expression in PTC and its predictive value for LN metastasis.

The incidence, presenting clinical findings and treatment patterns of Birdshot Retinochoroiditis in a high-prevalence region: findings from Northern Ireland, England and Wales.

BACKGROUND: Birdshot Retinochoroiditis (BSRC) is a rare, chronic posterior uveitis that is strongly associated with HLA-A*29.2 positivity. To date, no robust incidence studies of BSRC have been undertaken. We present the first epidemiological study of BSRC in a high-prevalence region. METHODS: In collaboration with the British Ophthalmological Surveillance Unit, all new cases of BSRC between May 2017 and June 2019 were prospectively collected. Presenting demographics, symptoms, signs and treatment modalities were collected. A follow-up questionnaire twelve months later was also sent. RESULTS: Thirty-seven confirmed cases meeting the reporting criteria were identified. Twenty-three cases had both baseline and follow-up data. The total population incidence of BSRC was 0.035 cases per 100,000 person-years [95% CI 0.025-0.048 cases per 100 000 people]. 97.3% were HLA-A*29 positive. The median age was 46 years, with females making up 78% of patients. There were no significant differences in the latitudinal incidence of BSRC. At presentation, floaters were the most common symptom. Optic disc swelling was the most common sign. Mean presenting visual acuity was independent of symptom duration. Combined systemic corticosteroids and immunomodulatory therapy were the most common treatments at baseline and follow-up. Intravitreal steroids were equally popular at follow-up. CONCLUSIONS: This study provides the first nationwide estimate of the incidence of BSRC in a high-prevalence region. Cases were more common in females, with a broad range of presentation ages. No significant latitudinal effect of incidence was identified. Systemic therapy with steroids and IMT remain the most common treatments.

Accuracy of real-time SNOMED-CT coding by clinicians in an urban tertiary emergency department: A retrospective cohort study.

OBJECTIVE: This study aimed to determine the accuracy of the reported diagnoses and procedures to the National non-Admitted Patient Collection (NNPAC) from Auckland City Hospital Adult Emergency Department, and whether there were disparities between Maori and non-Maori patients. METHODS: We audited 5788 (n = 594 Maori, 5194 non-Maori) visits in February 2021 to determine whether diagnoses and procedures were recorded and whether these were recorded differently for Maori compared to non-Maori. A random sample of case notes, stratified by five common chief presenting complaints (n = 114) were selected to compare clinician recording of diagnoses and procedures in real time, to those derived from the clinical notes by auditors blinded to the actual diagnosis and patient name and ethnicity. The New Zealand Emergency Department SNOMED-CT reference set was used to code diagnoses. RESULTS: Maori were less likely to have a diagnosis recorded when discharged from the ED compared to non-Maori, relative risk 1.48 (1.08, 2.04), p = 0.016 (n = 3045). Failure to record diagnoses was due to flaw in the system for extracting diagnoses from electronic notes, rather than failure to make a diagnosis. There was agreement in 111/114 cases for diagnosis: 53/56, 94.6% (95 %CI 85,99) for Maori, and 58/58, 100% (95 %CI 93,100) for non-Maori; p = 0.115. There was agreement in 60/114 cases for procedures completed: 31/56, 55.4% (95 %CI 42,66) for Maori, and 29/58, 50% (95 %CI 38,62) for non-Maori; p = 0.567. CONCLUSION: Maori were less likely to have a diagnosis recorded at discharge due to systemic bias in how we captured diagnoses electronically. Our system should change to remove this inequity. The diagnoses recorded using SNOMED-CT were mostly an accurate reflection of clinician's notes, while recording of procedures was poor.

Disposition disparities in an urban tertiary emergency department.

OBJECTIVE: To explore disparities between Maori and non-Maori patients with respect to triage acuity and disposition based on presenting complaint. METHODS: This was a retrospective review of 5788 (n = 594 Maori, n = 5194 non-Maori) ED visits in February 2021, extracted from the hospital data warehouse. RESULTS: Maori were triaged similarly to non-Maori but were less likely to be admitted compared to non-Maori: relative risk 0.87 (0.78, 0.97), P = 0.008. CONCLUSION: Maori were less likely to be admitted for similar presenting complaints, despite similar triage acuity. Further research is required to determine the reasons for this apparent inequity.

Advancing Our Understanding of Corneal Herpes Simplex Virus-1 Immune Evasion Mechanisms and Future Therapeutics.

Herpes stromal keratitis (HSK) is a disease that commonly affects the cornea and external eye and is caused by Herpes Simplex Virus type 1 (HSV-1). This virus infects approximately 66% of people worldwide; however, only a small portion of these people will develop symptoms in their lifetime. There is no cure or vaccine available for HSV-1; however, there are treatments available that aim to control the inflammation caused by the virus and prevent its recurrence. While these treatments are beneficial to those suffering with HSK, there is a need for more effective treatments to minimise the need for topical steroids, which can have harmful effects, and to prevent bouts of disease reactivation, which can lead to progressive corneal scarring and visual impairment. This review details the current understanding of HSV-1 infection and discusses potential novel treatment options including microRNAs, TLRs, mAbs, and aptamers.

Immunotherapy in hematological malignancies: recent advances and open questions.

Over recent years, tremendous advances in immunotherapy approaches have been observed, generating significant clinical progress. Cancer immunotherapy has been shown, in different types of blood cancers, to improve the overall survival of patients. Immunotherapy treatment of hematopoietic malignancies is a newly growing field that has been accelerating over the past years. Several US FDA approved drugs and cell-based therapies are being exploited in the late stage of clinical trials. This review attempt to highlight and discuss the numerous innovative immunotherapy approaches of hematopoietic malignancy ranging from nonmyeloablative transplantation, T-cell immunotherapy, natural killer cells and immune agonist to monoclonal antibodies and vaccination. In addition, a brief discussion on the future advances and accomplishments required to counterpart the current immunotherapeutic approaches for hematopoietic malignancies were also highlighted.

Mouse Periosteal Cell Culture, in vitro Differentiation, and in vivo Transplantationin Tibial Fractures.

The periosteum covering the outer surface of bone contains skeletal stem/progenitor cells that can efficiently form cartilage and bone during bone repair. Several methods have been described to isolate periosteal cells based on bone scraping and/or enzymatic digestion. Here, we describe an explant culture method to isolate periosteum-derived stem/progenitor cells for subsequent in vitro and in vivo analyses. Periosteal cells (PCs) isolated using this protocol express mesenchymal markers, can be expanded in vitro, and exhibit high regenerative potential after in vivo transplantation at a fracture site, suggesting that this protocol can be employed for PC production to use in new cell-based therapies.

Renal Capsule Transplantation to Assay Angiogenesis in Skeletal Development and Repair.

Renal capsule transplantation is a very helpful method to grow embryonic tissues or tumors in a vascular environment, allowing for long-term engraftment and biological analyses. This chapter describes the surgical procedure for the transplantation of embryonic skeletal elements in the renal capsule of adult mice and points out the manipulations that can be applied for assaying the role of angiogenesis during bone development and repair.

Herpes simplex virus 1 targets IRF7 via ICP0 to limit type I IFN induction.

Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV-1) infection, is the commonest cause of infectious blindness in the developed world. Following infection the virus is initially suspended in the tear film, where it encounters a multi-pronged immune response comprising enzymes, complement, immunoglobulins and crucially, a range of anti-viral and pro-inflammatory cytokines. However, given that HSV-1 can overcome innate immune responses to establish lifelong latency throughout a susceptible individual's lifetime, there is significant interest in understanding the mechanisms employed by HSV-1 to downregulate the anti-viral type I interferon (IFN) mediated immune responses. This study aimed to investigate the interactions between infected cell protein (ICP)0 and key elements of the IFN pathway to identify possible novel targets that contribute to viral immune evasion. Reporter gene assays demonstrated the ability of ICP0 to inhibit type I IFN activity downstream of pathogen recognition receptors (PRRs) which are known to be involved in host antiviral defences. Further experiments identified interferon regulatory factor (IRF)7, a driver of type I IFN, as a potential target for ICP0. These findings increase our understanding of the pathogenesis of HSK and suggest IRF7 as a potential therapeutic target.

Methods in Electrode Implantation and Wiring for Long-Term Continuous EEG Monitoring in Rodent Models of Epilepsy and Behavioral Disturbances.

Rodent seizure models that pathologically and behaviorally recapitulate age-tailored epileptic disorders are used by us and others to advance our understanding of the chronobiology and mechanisms of epileptic seizure emergence and their comorbidities and to investigate potential novel treatment strategies. Obtaining prolonged continuous electroencephalogram (EEG) tracings over months is essential in this line of translational research, particularly to assess the relation between electrographic changes and the development of seizures and their various psychiatric and cognitive comorbidities in models where seizures gradually emerge over weeks following brain insults. Here we describe our approach to electrode implantation and wiring in order to successfully obtain high-quality continuous EEG tracings in rats for prolonged periods. A detailed stepwise methodological description is provided with a special focus on the details that help most in avoiding notorious pitfalls such as premature EEG cable disconnections and a poor signal to noise ratio.

Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin.

Bone regeneration relies on the activation of skeletal stem cells (SSCs) that still remain poorly characterized. Here, we show that periosteum contains SSCs with high bone regenerative potential compared to bone marrow stromal cells/skeletal stem cells (BMSCs) in mice. Although periosteal cells (PCs) and BMSCs are derived from a common embryonic mesenchymal lineage, postnatally PCs exhibit greater clonogenicity, growth and differentiation capacity than BMSCs. During bone repair, PCs can efficiently contribute to cartilage and bone, and integrate long-term after transplantation. Molecular profiling uncovers genes encoding Periostin and other extracellular matrix molecules associated with the enhanced response to injury of PCs. Periostin gene deletion impairs PC functions and fracture consolidation. Periostin-deficient periosteum cannot reconstitute a pool of PCs after injury demonstrating the presence of SSCs within periosteum and the requirement of Periostin in maintaining this pool. Overall our results highlight the importance of analyzing periosteum and PCs to understand bone phenotypes.

Coupling between Myogenesis and Angiogenesis during Skeletal Muscle Regeneration Is Stimulated by Restorative Macrophages.

In skeletal muscle, new functions for vessels have recently emerged beyond oxygen and nutrient supply, through the interactions that vascular cells establish with muscle stem cells. Here, we demonstrate in human and mouse that endothelial cells (ECs) and myogenic progenitor cells (MPCs) interacted together to couple myogenesis and angiogenesis in vitro and in vivo during skeletal muscle regeneration. Kinetics of gene expression of ECs and MPCs sorted at different time points of regeneration identified three effectors secreted by both ECs and MPCs. Apelin, Oncostatin M, and Periostin were shown to control myogenesis/angiogenesis coupling in vitro and to be required for myogenesis and vessel formation during muscle regeneration in vivo. Furthermore, restorative macrophages, which have been previously shown to support myogenesis in vivo, were shown in a 3D triculture model to stimulate myogenesis/angiogenesis coupling, notably through Oncostatin M production. Our data demonstrate that restorative macrophages orchestrate muscle regeneration by controlling myogenesis/angiogenesis coupling.

The Spindle Assembly Checkpoint Safeguards Genomic Integrity of Skeletal Muscle Satellite Cells.

To ensure accurate genomic segregation, cells evolved the spindle assembly checkpoint (SAC), whose role in adult stem cells remains unknown. Inducible perturbation of a SAC kinase, Mps1, and its downstream effector, Mad2, in skeletal muscle stem cells shows the SAC to be critical for normal muscle growth, repair, and self-renewal of the stem cell pool. SAC-deficient muscle stem cells arrest in G1 phase of the cell cycle with elevated aneuploidy, resisting differentiation even under inductive conditions. p21(CIP1) is responsible for these SAC-deficient phenotypes. Despite aneuploidy's correlation with aging, we find that aged proliferating muscle stem cells display robust SAC activity without elevated aneuploidy. Thus, muscle stem cells have a two-step mechanism to safeguard their genomic integrity. The SAC prevents chromosome missegregation and, if it fails, p21(CIP1)-dependent G1 arrest limits cellular propagation and tissue integration. These mechanisms ensure that muscle stem cells with compromised genomes do not contribute to tissue homeostasis.

Role of muscle stem cells during skeletal regeneration.

Although the importance of muscle in skeletal regeneration is well recognized clinically, the mechanisms by which muscle supports bone repair have remained elusive. Muscle flaps are often used to cover the damaged bone after traumatic injury yet their contribution to bone healing is not known. Here, we show that direct bone-muscle interactions are required for periosteum activation and callus formation, and that muscle grafts provide a source of stem cells for skeletal regeneration. We investigated the role of satellite cells, the muscle stem cells. Satellite cells loss in Pax7(-/-) mice and satellite cell ablation in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice impaired bone regeneration. Although satellite cells did not contribute as a large source of cells endogenously, they exhibited a potential to contribute to bone repair after transplantation. The fracture healing phenotype in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice was associated with decreased bone morphogenetic proteins (BMPs), insulin-like growth factor 1, and fibroblast growth factor 2 expression that are normally upregulated in response to fracture in satellite cells. Exogenous rhBMP2 improved bone healing in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice further supporting the role of satellite cells as a source of growth factors. These results provide the first functional evidence for a direct contribution of muscle to bone regeneration with important clinical implications as it may impact the use of muscle flaps, muscle stem cells, and growth factors in orthopedic applications.

Cellular and molecular bases of skeletal regeneration: what can we learn from genetic mouse models?

Although bone repairs through a very efficient regenerative process in 90% of the patients, many factors can cause delayed or impaired healing. To date, there are no reliable biological parameters to predict or diagnose bone repair defects. Orthopedic surgeons mostly base their diagnoses on radiographic analyses. With the recent progress in our understanding of the bone repair process, new methods may be envisioned. Animal models have allowed us to define the key steps of bone regeneration and the biological and mechanical factors that may influence bone healing in positive or negative ways. Most importantly, small animal models such as mice have provided powerful tools to apprehend the genetic bases of normal and impaired bone healing. The current review presents a state of the art of the genetically modified mouse models that have advanced our understanding of the cellular and molecular components of bone regeneration and repair. The review illustrates the use of these models to define the role of inflammation, skeletal cell lineages, signaling pathways, the extracellular matrix, osteoclasts and angiogenesis. These genetic mouse models promise to change the field of orthopedic surgery to help establish genetic predispositions for delayed repair, develop models of non-union that mimic the human conditions and elaborate new therapeutic approaches to enhance bone regeneration.

Renal capsule transplantations to assay skeletal angiogenesis.

Renal capsule transplantation is a very helpful method to grow embryonic tissues or tumors in a vascular environment, allowing long-term engraftment and biological analyses. This chapter describes the surgical procedure for the transplantation of embryonic skeletal elements in the renal capsule of adult mice and points out the manipulations that can be applied for assaying the role of angiogenesis during bone development.

Delayed bone regeneration is linked to chronic inflammation in murine muscular dystrophy.

Duchenne muscular dystrophy (DMD) patients exhibit skeletal muscle weakness with continuous cycles of muscle fiber degeneration/regeneration, chronic inflammation, low bone mineral density, and increased risks of fracture. Fragility fractures and associated complications are considered as a consequence of the osteoporotic condition in these patients. Here, we aimed to establish the relationship between muscular dystrophy and fracture healing by assessing bone regeneration in mdx mice, a model of DMD with absence of osteoporosis. Our results illustrate that muscle defects in mdx mice impact the process of bone regeneration at various levels. In mdx fracture calluses, both cartilage and bone deposition were delayed followed by a delay in cartilage and bone remodeling. Vascularization of mdx fracture calluses was also decreased during the early stages of repair. Dystrophic muscles are known to contain elevated numbers of macrophages contributing to muscle degeneration. Accordingly, we observed increased macrophage recruitment in the mdx fracture calluses and abnormal macrophage accumulation throughout the process of bone regeneration. These changes in the inflammatory environment subsequently had an impact on the recruitment of osteoclasts and the remodeling phase of repair. Further damage to the mdx muscles, using a novel model of muscle trauma, amplified both the chronic inflammatory response and the delay in bone regeneration. In addition, PLX3397 treatment of mdx mice, a cFMS (colony stimulating factor receptor 1) inhibitor in monocytes, partially rescued the bone repair defect through increasing cartilage deposition and decreasing the number of macrophages. In conclusion, chronic inflammation in mdx mice contributes to the fracture healing delay and is associated with a decrease in angiogenesis and a transient delay in osteoclast recruitment. By revealing the role of dystrophic muscle in regulating the inflammatory response during bone repair, our results emphasize the implication of muscle in the normal bone repair process and may lead to improved treatment of fragility fractures in DMD patients.

Human and murine skeletal muscle reserve cells.

Study of stem cell phenotype and functions requires their proper isolation. Stem cells isolated from skeletal muscle are a useful tool to explore molecular pathways involved in the regulation of myogenesis. Among progenitor cells, a subset of cells, called reserve cells, has been identified, in vitro, in myogenic cell cultures. This subset of cells remains undifferentiated while the main population of progenitor cells commits to terminal myogenic differentiation. When replated, these reserve cells grow as new colonies of progenitors. At the time of differentiation, they reform both differentiated myotubes and undifferentiated reserve cells. Here, we present a protocol to obtain and further isolate reserve cells from both human and murine myogenic cell cultures, together with techniques to analyze their cell cycle status.