The use of cap-mounted clips as a primary hemostatic modality in nonvariceal upper gastrointestinal bleeding: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Cap-mounted-clips, especially Over-The-Scope-Clip (OTSC™), are recommended for recurrent nonvariceal upper gastrointestinal bleeding (NVUGIB). There has been recent interest in their use as an initial hemostatic modality. We performed a systematic review of randomized controlled trials (RCTs) assessing cap-mounted clips' efficacy as a primary hemostatic modality in NVUGIB. METHODS: A literature search of MEDLINE, EMBASE, and ISI Web of Science databases up to April 2024 identified RCTs comparing cap-mounted clips to standard endoscopic therapy (SET) as a primary hemostatic modality in NVUGIB. The primary endpoint was the composite outcome of further bleeding (persistent or recurrent) at 30 days. Secondary outcomes included persistent bleeding at index endoscopy and 30-day rebleeding, individually. Other pertinent outcomes were also recorded. A meta-analysis was performed to determine pooled risk ratios (RRs), comparing cap-mounted clip to SET. Out of 516 citations, five RCTs (n = 555), all assessing OTSC™, were included. RESULTS: The composite outcome of further bleeding was lower with cap-mounted clip versus SET (RR = 0.33 [95% confidence interval {CI}: 0.20-0.54]). There was no difference in persistent bleeding at initial endoscopy (RR = 0.30 [95% CI: 0.07-1.30]), but 30-day rebleeding was lower with cap-mounted clip (RR = 0.38 [95% CI: 0.21-0.70]). There were no differences in other outcomes. Grading of the evidence ranged from very low to moderate, mainly due to risk of bias and imprecision. CONCLUSIONS: Cap-mounted clips may be an efficacious primary hemostatic modality, associated with a lower further bleeding at 30 days compared to SET in NVUGIB. However, due to limitations in existing evidence, further research must better characterize an optimal subgroup of patients benefiting most from this approach before adopting its routine use.

FRACTION: protocol of a phase II study of Fedratinib and Nivolumab combination in patients with myelofibrosis and resistance or suboptimal response to JAK-inhibitor treatment of the German MPN study group (GSG-MPN).

Development of Janus-kinase (JAK) inhibitors has revolutionized the therapeutic landscape for patients with myeloproliferative neoplasia (MPN). Following approval of the first JAK1/2-inhibitor Ruxolitinib, symptoms of this inflammatory disease, characterized by splenomegaly, release of inflammatory cytokines and appearance of thrombosis, could be effectively reduced for the first time. However, JAK-inhibitor treatment is limited in several aspects: 1) duration of response: 3 years after initiation of therapy more than 50% of patients have discontinued JAK-inhibitor treatment due to lack of efficacy or resistance; 2) reduction of disease burden: while effective in reducing inflammation and constitutional symptoms, JAK-inhibitors fail to reduce the malignant clone in the majority of patients and therefore lack long-term efficacy. Early clinical trials for patients with myelofibrosis (MF) have tried to address these issues for patients with suboptimal response to Ruxolitinib therapy while combination therapies with Fedratinib are rare. Recent reports provided first evidence on how the JAK2-V617F mutated myeloid cells may influence T-cell responses. JAK2-V617F promoted the synthesis of PD-L1 in MPN cells leading to limited anti-neoplastic T-cell responses, metabolic changes in T-cells and eventually JAK2-V617F-driven immune-escape of MPN cells. These findings may facilitate the use of immunotherapeutic approaches for JAK-mutated clones. Immune checkpoints refer to a variety of inhibitory pathways that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. The FRACTION study is a single arm, open label Phase II trial investigating the combination of Fedratinib with the PD-1 inhibitor Nivolumab in patients with myelofibrosis and suboptimal or lack of response to JAK-inhibitor therapy. Over a 12 months period the trial assesses longer term outcomes, particularly the effects on clinical outcomes, such as induction of clinical remissions, quality of life and improvement of anemia. No prospective clinical trial data exist for combinations of JAK- and immune-checkpoint-inhibitors in the planned MF study population and this study will provide new findings that may contribute to advancing the treatment landscape for MF patients with suboptimal responses and limited alternatives.

Steady-State Versus Chemotherapy-Based Stem Cell Mobilization in Multiple Myeloma: A Single-Center Study to Analyze Efficacy and Safety.

Background: High-dose chemotherapy followed by autologous hematopoietic stem cell support is recommended in the treatment of eligible multiple myeloma (MM) patients. The aim of this study was to compare the efficacy and safety of steady-state versus chemotherapy-based stem cell mobilization in our Hungarian patient population. Methods: The subjects were 210 MM patients who underwent stem cell mobilization procedure between 2018 and 2022. Solo granulocyte colony-stimulating factor (G-CSF) was administered in 104 cases, while 106 patients received chemotherapy which was followed by G-CSF administration. We evaluated the ratio of successful mobilizations, the amount of collected stem cells, the incidence of infections and cost-effectivity in the two groups. Results: In the steady-state group, there was a significantly higher need for plerixafor (45% vs. 13%, P < 0.001), unsuccessful stem cell mobilization was more frequent (11% vs. 3%, P = 0.024) and the mean amount of collected stem cells was lower (6.9 vs. 9.8 × 106, P < 0.001) than in the chemotherapy group. However, infections were less frequent (4% vs. 27%, P < 0.001) and the number of days spent in hospital was significantly lower (6 vs. 14 days, P < 0.001). Plerixafor was more frequently administered in those who had received lenalidomide or daratumumab than in those who had been treated with other regimens (41% vs. 23%, P = 0.007 and 78% vs. 23%, P < 0.001, respectively). Conclusions: Steady-state mobilization is a safe method; however, the higher rate of plerixafor administration and unsuccessful attempts may question its superiority to chemomobilization.

Factors affecting early antibiotic delivery in open tibial shaft fractures.

INTRODUCTION: The incidence of infection in open tibial shaft injuries varies with the severity of the injury with rates ranging from roughly 2% for Gustilo-Anderson type I to nearly 43% for type IIIB fractures. As with all fractures, timely antibiotics administration in the emergency department (ED) is an essential component of fracture management and infection prevention. This study identifies factors associated with the expedient administration of antibiotics for open tibial shaft fractures. METHODS: This retrospective study identified patients treated for open tibial shaft fractures at an academic level 1 trauma center between 2015 and 2021. Open fractures were identified by reviewing patient charts. We used chart reviews to gather demographics, fracture characteristics, postoperative outcomes, trauma activation, and time to antibiotic order, delivery, and operating room. Univariate analysis was used to compare patients who received antibiotics within 1 h of ED presentation to those who did not. Multivariate analysis was performed to investigate factors associated with faster delivery of antibiotics. RESULTS: Among 70 ED patients with open tibial shaft fractures, 39 (56%) received early administration of antibiotics. Arrival at the ED via emergency medical service (EMS) as opposed to walking in (98% vs. 74%, p = 0.01) and trauma activation (90% vs. 52%, p < 0.001) were significantly more common in the early administration group than the late group. The early group had shorter intervals between antibiotic order and delivery (0.02 h vs. 0.35 h, p = 0.007). Multivariate analysis suggested that trauma activation, EMS arrival, and arrival during non-overnight shifts were independent predictors of a shorter time to antibiotic administration (odds ratios 11.9, 30.7, and 5.4, p = 0.001, 0.016, and 0.013, respectively). DISCUSSION: Earlier antibiotic delivery is associated with non-overnight arrival at the ED, arrival via EMS, and a coordinated trauma activation. Our findings indicate that in cases where administering antibiotics is critical to achieving positive outcomes, it is advisable to initiate a coordinated trauma response. Furthermore, hospital personnel should be attentive to the need for rapid administration of antibiotics to patients with open fractures who arrive via walk-in or during late-night hours.

Surgical repair of endoscopy-induced colonic perforations: a case-matched study of short-term morbidity and mortality.

BACKGROUND: Our aim was to describe the clinical outcomes of surgical interventions performed for the management of colonoscopy-related perforations and to compare these outcomes with those of matched colorectal surgeries performed in elective and emergency settings. METHODS: We included patients with endoscopic colonic perforation who underwent surgical intervention from the 2014-2017 National Surgery Quality Improvement Program participant use data colorectal targeted procedure file. The primary outcome in this study was short term surgical morbidity and mortality. Patients (group 1) were matched with 1:2 ratio to control patients undergoing same surgical interventions for other indications on an elective (group 2) or emergency basis (group 3). Bivariate analysis was conducted to compare categorical variables between the three groups, and multivariate logistic regression was used to evaluate the association between the surgical indication and 30-day postoperative outcomes. RESULTS: A total of 590 patients were included. The average age of the patients was 66.5±13.6 with female gender predominance (381, 64.6%) The majority of patients underwent open colectomy (365, 61.9%) while the rest had suturing (140, 23.7%) and laparoscopic colectomy (85, 14.4%). Overall mortality occurred in 4.1% and no statistically significant difference in mortality was found between the three techniques (P=0.468). Composite morbidity occurred in 163 patients (27.6%). It was significantly lower in laparoscopic colectomy (14.1%) compared to 30.2% and 29.4% in open colectomy and suturing approaches (P=0.014). Patients undergoing colectomy for iatrogenic colonic perforation had less mortality, infection rates and sepsis, as well as bleeding episodes compared to those who had colectomy on an emergent basis. Outcomes were comparable between the former group and patients undergoing elective colectomy for other indications. CONCLUSIONS: Surgical management of colonoscopy related perforations is safe and effective with outcomes that are similar to that of patients undergoing elective colectomy.

Peptic ulcer disease.

Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake of some medications (such as aspirin and non-steroidal anti-inflammatory medications), or being critically ill (stress-related), or it can be idiopathic. The clinical presentation is usually uncomplicated, with peptic ulcer disease management based on eradicating H pylori if present, the use of acid-suppressing medications-most often proton pump inhibitors (PPIs)-or addressing complications, such as with early endoscopy and high-dose PPIs for peptic ulcer bleeding. Special considerations apply to patients on antiplatelet and antithrombotic agents. H pylori treatment has evolved, with the choice of regimen dictated by local antibiotic resistance patterns. Indications for primary and secondary prophylaxis vary across societies; most suggest PPIs for patients at highest risk of developing a peptic ulcer, its complications, or its recurrence. Additional research areas include the use of potassium-competitive acid blockers and H pylori vaccination; the optimal approach for patients at risk of stress ulcer bleeding requires more robust determinations of optimal patient selection and treatment selection, if any. Appropriate continuation of PPI use outweighs most possible side-effects if given for approved indications, while de-prescribing should be trialled when a definitive indication is no longer present.

The role of internal architecture in producing high-strength 3D printed cobalt-chromium objects.

PURPOSE: The objectives of the current study were to estimate the influence of self-reinforced hollow structures with a graded density on the dimensional accuracy, weight, and mechanical properties of Co-Cr objects printed with the direct metal laser sintering (DMLS) technique. MATERIALS AND METHODS: Sixty-five dog-bone samples were manufactured to evaluate the dimensional accuracy of printing, weight, and tensile properties of DMLS printed Co-Cr. They were divided into Group 1 (control) (n = 5), Group 2, 3, and 4 with incorporated hollow structures based on (spherical, elliptical, and diamond) shapes; they were subdivided into subgroups (n = 5) according to the volumetric reduction (10%, 15%, 20% and 25%). Radiographic imaging and microscopic analysis of the fractographs were conducted to validate the created geometries; the dimensional accuracy, weight, yield tensile strength, and modulus of elasticity were calculated. The data were estimated by one-way ANOVA and Duncan's tests at P < .05. RESULTS: The accuracy test showed an insignificant difference in the x, y, z directions in all printed groups. The weight was significantly reduced proportionally to the reduced volume fraction. The yield strength and elastic modulus of the control group and Group 2 at 10% volume reduction were comparable and significantly higher than the other subgroups. CONCLUSION: The printing accuracy was not affected by the presence or type of the hollow geometry. The weight of Group 2 at 10% reduction was significantly lower than that of the control group. The yield strength and elastic modulus of the Group 2 at a 10% reduction showed means equivalent to the compact objects and were significantly higher than other subgroups.

Endoscopic management of intraprocedural bleeding during endoscopic interventions.

Endoscopic resection techniques have evolved over time, allowing effective and safe resection of the majority of pre-malignant and early cancerous lesions in the gastrointestinal tract. Bleeding is one of the most commonly encountered complications during endoscopic resection, which can interfere with the procedure and result in serious adverse events. Intraprocedural bleeding is relatively common during endoscopic resection and, in most cases, is a mild and self-limiting event. However, it can interfere with the completion of the resection and may result in negative patient-related outcomes in severe cases, including the need for hospitalization and blood transfusion as well as the requirement for radiological or surgical interventions. Appropriate management of intraprocedural bleeding can improve the safety and efficacy of endoscopic resection, and it can be readily achieved with the use of several endoscopic hemostatic tools. In this review, we discuss the recent advances in the approach to intraprocedural bleeding complicating endoscopic resection, with a focus on the various endoscopic hemostatic tools available to manage such events safely and effectively.

Gonococcal peritonitis: A case report and review of literature.

Neisseria gonorrhoeae (Ng) is a major cause of morbidity among sexually active individuals, occasionally leading to serious complications if left untreated. We describe a case of gonococcal peritonitis as a rare complication of Ng infection in a woman presenting with acute abdomen and intestinal subacute occlusion. Due to the rarity of this clinical presentation, we review the scientific literature to identify best practices and inform guidelines.

The influence of internally architected voids in the creation of high-strength, low-weight 3D-printed cobalt-chromium prototypes.

Background: The additive manufacturing technology made the topology optimization technique feasible. This technique can indefinitely reduce the weight of the printed items with a promising increase in the mechanical properties of that item. Materials and Methods: In the current experimental study, 50 samples were fabricated for a 3-point bending test. They were divided into (n = 5) as a control Group 1 free of internal geometries, (n = 15) for each of Groups 2-4, and they were subdivided into (n = 5) for each percentage of reduction per volume (10%, 15%, and 20%). Spherical, ovoid, and diamond shapes were each group's fundamental geometries, respectively. Cylindrical tunnels connected the voids in each group. Radiographic images were performed to validate the created geometries, the weight was measured, and flexural strength and modulus of elasticity were calculated. Data were analyzed by one-way ANOVA and Duncan's post hoc tests at P < 0.05. Results: The weight results showed a significant reduction in mass. The flexural strength of Group 2 at a 10% reduction per volume had the highest mean significantly without compromising the elastic modulus. In comparison, the means of group 4 at 20% reduction showed the lowest level of toughness. Conclusion: The weight was reduced according to the reduction percentage. The flexural strength of Group 2 at a 10% reduction showed the highest degree of toughness among all groups. The void shape and density influenced the mechanical properties tested.

Microsnare retrieval as a bail-out technique of Detached Woven EndoBridge device: Illustrative series.

BACKGROUND: The Woven EndoBridge (WEB) device (MicroVention, Tustin, CA, USA) has an excellent safety profile. While major complications such as device malposition and migration are rare, they can have serious consequences if not addressed promptly. Our case series describes the safety and efficacy of Amplatz goose neck microsnare device (Medtronic in Irvine, CA, USA) in endovascular retrieval of a detached WEB device. METHODS: We retrospectively reviewed six consecutive patients who underwent endovascular WEB retrieval using Amplatz microsnare device between March 2012 and December 2022. RESULTS: All six WEB devices were successfully retrieved either directly from the aneurysm sac due to device malpositioning or from a distal branch following device migration. None of the patients experienced intra-operative aneurysm perforation, arterial dissection, or vasospasm attributable to the process of WEB extraction. Five out of six patients (83.3%) had a good functional outcome (mRS 0-1) upon discharge from the hospital and at 24 months. CONCLUSION: Our experience suggests that detached WEB devices can be safely retrieved using an Amplatz microsnare. Apart from addressing device migration, direct removal of an undersized or malpositioned WEB from the aneurysm sac appears to be a safe option that can be considered when all other rescue techniques have been exhausted.

Excision of Solitary Non-syndromic Oral Plexiform Neurofibroma Utilizing a Diode Laser: A Case Report.

Plexiform neurofibroma is a benign peripheral nerve sheath tumor known to be pathognomonic for neurofibromatosis type 1. However, solitary plexiform neurofibroma in the oral cavity is extremely rare. Herein, we presented a 73-year-old Saudi male with solitary plexiform neurofibroma located on the maxillary alveolar ridge, which was excised successfully using a 940 nm diode laser. Microscopic examination revealed a multinodular arrangement of benign spindle cells in a haphazard pattern. Immunohistochemical analysis showed positive staining for S100 and CD34 in the tumor cells.

Medical Students Understanding of The Scope of Plastic Surgery.

Background Plastic surgery has developed to benefit in a variety of challenging areas formerly handled by other disciplines. Medical students do not have a clear picture of plastic surgery as a career due to lacking scope, clinical practice, and understanding of plastic surgery as a clinical area of expertise, including general practitioners, nursing staff, medical trainees, and the general public, and misconceptions about the extent of reconstructive and plastic surgery. Methods A cross-sectional observational study was conducted on Kuwait University Medical students (2nd-7th Years) over a period of 1 month. A questionnaire and a consent form were provided to eligible students. The inclusion criteria were Kuwait University Medical students from 2nd to 7th Years with signed consent form. The response was collected via email sent in coordination with the Vice Dean of Student Affairs in the Faculty of Medicine. Using statistical package for the social sciences, responses were statistically analyzed. Pearson's chi-square test was used to calculate p -values, where p < 0.05 was considered statistically significant. Results A total of 244 eligible medical students, 121 males and 123 females, were included in the study, with a mean age of 21 (±2) years. Similarly, 126 (51.6%) were preclinical students (2nd-4th-year students), while 118 (48.4%) were clinical students (5th-7th-year students). About 79.8% of medical students believed that plastic surgery plays an essential role in trauma management, whereas 9.2% did not consider plastic surgery significant for trauma management. This study found that only 15.5% of medical students were interested in enrolling in plastic surgery residency after graduation, while 47.1% of students did not consider plastic surgery residency after graduation. However, 37.4% were uncertain. The two most driving factors in deciding on plastic surgery residency were expected income (61.8%) and lifestyle (14.3%). Conclusion Improving medical students' education quality can enhance their perception and awareness of plastic surgery. Students should be taught the broader scope of plastic surgery. The inclusion of formal training during undergraduation is the essence of time and should be added to or improved during plastic surgery rotations with more emphasis on reconstructive and hand/peripheral nerve surgery. Student-led interest groups can be a useful tool for educating students about their specialty.

The Prevalence and Associated Risk Factors for Neonatal Thrombocytopenia Among Newborns Admitted to the Neonatal Intensive Care Unit.

Background Thrombocytopenia is the most prevalent hematological condition in neonates that develops in the neonatal intensive care unit (NICU). This set of illnesses is caused by either decreased platelet production due to placental insufficiency, increased platelet breakdown (consumption), or a combination of the two causes. Based on platelet count, it is defined as mild, moderate, or severe thrombocytopenia, with early and late onset. Purpose The purpose of this study is to determine the prevalence of thrombocytopenia and the factors that contribute to it in newborns hospitalized in the neonatal critical care unit at the Maternity and Children Hospital in Al Ahsa, Saudi Arabia. Methods This descriptive retrospective cross-sectional study was carried out at the NICU of the Maternity and Children Hospital in Al Ahsa, Saudi Arabia, over the span of one year (August 2022 to August 2023) among hospitalized neonates with thrombocytopenia. Thrombocytopenia is defined as a platelet count of 150,000 or less. These patients were monitored until they recovered or died. Results The inclusion criteria were met by a total of 242 newborns with thrombocytopenia. Half of the neonates (57%) were full-term, with Apgar scores greater than 5 at the first (84%) and fifth (93%) minutes, respectively. The great majority of individuals (84%) experienced early-onset thrombocytopenia of mild severity (62%) and were asymptomatic (93%). The majority of the cases resolved spontaneously, with only 21% requiring platelet transfusion. There was a significant relationship discovered between gestational age and the severity of thrombocytopenia, with very preterm infants having moderate to severe thrombocytopenia, as well as birth weight (p=0.001). Furthermore, neonates with severe thrombocytopenia had a considerably higher mortality rate (p=0.001). Conclusion The mortality and morbidity of newborns with perinatal risk for neonatal thrombocytopenia can be reduced with timely detection of the cause and development of thrombocytopenia, as well as adequate and early care.

PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis.

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options.

Interferon-based therapies, such as ropeginterferon alfa-2b have emerged as promising disease-modifying agents for myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). Current ET treatments aim to normalize hematological parameters and reduce the thrombotic risk, but they do not modify the natural history of the disease and hence, have no impact on disease progression. Ropeginterferon alfa-2b (trade name BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval, has demonstrated a robust and sustained efficacy in polycythemia vera (PV) patients. Given the similarities in disease pathophysiology and treatment goals, ropeginterferon alfa-2b holds promise as a treatment option for ET. The ROP-ET trial is a prospective, multicenter, single-arm phase III study that includes patients with ET who are intolerant or resistant to, and/or are ineligible for current therapies, such as hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman, leaving these patients with limited treatment options. The primary endpoint is a composite response of hematologic parameters and disease-related symptoms, according to modified European LeukemiaNet (ELN) criteria. Secondary endpoints include improvements in symptoms and quality of life, molecular response and the safety profile of ropeginterferon alfa-2b. Over a 3-year period the trial assesses longer term outcomes, particularly the effects on allele burden and clinical outcomes, such as disease-related symptoms, vascular events and disease progression. No prospective clinical trial data exist for ropeginterferon alfa-2b in the planned ET study population and this study will provide new findings that may contribute to advancing the treatment landscape for ET patients with limited alternatives. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2023-505160-12-00; Registered on October 30, 2023.

Prognostic impact of the bone marrow tumor microenvironment, HLA-I and HLA-Ib expression in MDS and CMML progression to sAML.

Genetic aberrations and immune escape are fundamental in MDS and CMML initiation and progression to sAML. Therefore, quantitative and spatial immune cell organization, expression of immune checkpoints (ICP), classical human leukocyte antigen class I (HLA-I) and the non-classical HLA-Ib antigens were analyzed in 274 neoplastic and 50 non-neoplastic bone marrow (BM) biopsies using conventional and multiplex immunohistochemistry and correlated to publicly available dataset. Higher numbers of tissue infiltrating lymphocytes (TILs) were found in MDS/CMML (8.8%) compared to sAML (7.5%) and non-neoplastic BM (5.3%). Higher T cell abundance, including the CD8+ T cell subset, inversely correlated with the number of pathogenic mutations and was associated with blast BM counts, ICP expression, spatial T cell distribution and improved patients' survival in MDS and CMML. In MDS/CMML, higher PD-1/PD-L1/PD-L2 and HLA-I, but lower HLA-G expression correlated with a significantly better patients' outcome. Moreover, a closer spatial proximity of T cell subpopulations and their proximity to myeloid blasts showed a stronger prognostic impact when compared to TIL numbers. In sAML - the continuum of MDS and CMML - the number of TILs had no impact on prognosis, but higher CD28 and HLA-I expression correlated with a better outcome of sAML patients. This study underlines the independent prognostic value of the tumor microenvironment in MDS/CMML progression to sAML, which shows the most pronounced immune escape. Moreover, new prognostic markers, like HLA-G expression and spatial T cell distribution, were described for the first time, which might also serve as therapeutic targets.

Assessment, Resuscitation and Medical Management of Variceal and Nonvariceal Gastrointestinal Bleeding.

Upper gastrointestinal bleeding (UGIB) continues to be an important cause for emergency room visits and carries significant morbidity and mortality. Early resuscitative measures form the basis of the management of patients presenting with UGIB and can improve the outcomes of such patients including lowering mortality. In this review, using an evidence-based approach, we discuss the initial assessment and resuscitation of patients presenting with UGIB including identifying clues from history and physical examination to confirm UGIB, preendoscopic risk assessment tools, the role of early fluid resuscitation, utilization of blood products, use of pharmacologic interventions, and the optimal timing of endoscopy.

The impact of coronavirus crisis on human interpersonal relationships among AlAhsa population.

Background: Home quarantine during the coronavirus disease 2019 pandemic was a clear cause of loss of communication and a lot of conflicts between individuals, which had adverse consequences on people's relationships. Objective: This study aims to assess the effect of lockdown on interpersonal relationships in AlAhsa community. Methods: A.cross-sectional study was conducted during 2020-2021 with 306 participants in AlAhsa, the eastern region of Saudi Arabia. The data were collected using an online survey to explore the effect of lockdown on interpersonal relationships. Results: The study demonstrates that (61.8%) of the participants reported that their relationships were affected during lockdown, (61.4%) of them were affected negatively, with a higher rate among the unemployed and students (73.1%) and (64.8%), respectively. About 38.6% of the individuals were positively affected. Conclusion: Most of the participants identified that quarantine affected their interpersonal relationships negatively, which were impacted variably by different demographical statuses.

Résumé Contexte: La quarantaine à domicile pendant la pandémie de la maladie à coronavirus 2019 a été une cause évidente de perte de communication et de nombreux conflits entre individus, ce qui a eu des conséquences néfastes sur les relations interpersonnelles des gens. Objectif: Cette étude vise à évaluer l'effet du confinement sur les relations interpersonnelles dans la communauté d'AlAhsa. Méthodes: Une étude transversale a été menée de 2020 à 2021 avec 306 participants à AlAhsa, dans la région est de l'Arabie saoudite. Les données ont été collectées à l'aide d'une enquête en ligne afin d'explorer l'effet du confinement sur les relations interpersonnelles. Résultats: L'étude démontre que (61,8 %) des participants ont déclaré que leurs relations ont été affectées pendant le confinement, (61,4 %) d'entre eux ont été affectés négativement, avec un taux plus élevé parmi les chômeurs et les étudiants (73,1 %) et (64,8 %), respectivement. Environ 38,6 % des individus ont été affectés positivement. Conclusion: La plupart des participants ont identifié que la quarantaine a eu un impact négatif sur leurs relations interpersonnelles, impactées de manière variable par différents statuts démographiques. Mots-clés: Maladie à coronavirus 2019, relations interpersonnelles, Arabie saoudite.

Current perspectives on fenugreek bioactive compounds and their potential impact on human health: A review of recent insights into functional foods and other high value applications.

Despite long-standing uses in several food and medicine traditions, the full potential of the leguminous crop fenugreek (Trigonella foenum-graecum L.) remains to be realized in the modern diet. Not only its seeds, which are highly prized for their culinary and medicinal properties, but also its leaves and stems abound in phytochemicals with high nutritional and health promoting attributes. Fenugreek dual food-medicine applications and reported metabolic activities include hypoglycemic, antihyperlipidemic, antioxidative, anti-inflammatory, antiatherogenic, antihypertensive, anticarcinogenic, immunomodulatory, and antinociceptive effects, with potential organ-protective effects at the cardiovascular, digestive, hepatic, endocrine, and central nervous system levels. Effectiveness in alleviating certain inflammatory skin conditions and dysfunctions of the reproductive system was also suggested. As a food ingredient, fenugreek can enhance the sensory, nutritional, and nutraceutical qualities of a wide variety of foods. Its high nutritive density can assist with the design of dietary items that meet the demand for novelty, variety, and healthier foods. Its seeds provide essential protective nutrients and other bioactive compounds, notably galactomannans, flavonoids, coumarins, saponins, alkaloids, and essential oils, whose health benefits, alone or in conjunction with other bioactives, are only beginning to be tapped into in the food industries. This review summarizes the current state of evidence on fenugreek potential for functional food development, focusing on the nutrients and non-nutrient bioactive components of interest from a dietary perspective, and their applications for enhancing the functional and nutraceutical value of foods and beverages. New developments, safety, clinical evidence, presumed mechanisms of action, and future perspectives are discussed. HIGHLIGHTS: Fenugreek seeds and leaves have long-standing uses in the food-medicine continuum. Fenugreek phytochemicals exert broad-spectrum biological and pharmacological activities. They show high preventive and nutraceutical potential against common chronic diseases. Current evidence supports multiple mechanisms of action mediated by distinct bioactives. Opportunities for fenugreek-based functional foods and nutraceuticals are expanding.