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Fatma M Abdelaziz, Mahmoud Ahmed Kamal, Mohamed M Said, Mostafa M Diab Department of Ophthalmology, Faculty of Medicine, Fayoum University, Al Fayoum, EgyptCorrespondence: Mostafa M DiabDepartment of Ophthalmology, Faculty of Medicine, Fayoum University, 12 George Nirose St, Al Mesalla, Fayoum, Al Fayoum 63514, EgyptTel +20 842152290Email Mmd11@fayoum.edu.egPurpose: To compare the outcomes of anterior lamellar recession (ALR) versus posterior lamellar tarsal rotation (PLTR) procedure for the repair of lower eyelid trachomatous trichiasis (TT).Design: Prospective randomized comparative trial.Methods: Study Population and Interventions: Patients with lower eyelid TT were enrolled. Patients with a history of lower lid surgery, marked horizontal lid laxity, another evident cause for the trichiasis, and those under 18 years were excluded. Participants were randomized to either PLTR or ALR. The sequence was computer-generated by an independent statistician, and the allocation sequence was concealed in sealed opaque envelops. Patients were evaluated at 1 week and 1, 3, 6, and 12 months. Main Outcome Measures: postoperative trachomatous trichiasis (PTT) and cosmetic satisfaction.Results: A total of 60 patients were randomly assigned with 30 patients in each group. Two (3.3%) participants in PLTR group did not follow up and were excluded from the analysis. At 1, 3, and 6 months, PTT was significantly more frequent in the PLTR group than the ALR group (14.3% vs 0%; p= 0.048, 25% vs 0%; p= 0.004, 35.7% vs 10%; p= 0.019, respectively). In the ALR group, 6 patients (20%) had PTT at their 12-month follow-up visit compared with 15 patients (53.6%) in the PLTR group (P = 0.008) with absolute risk reduction of 33.6% (95% (CI= 9% − 58%)). Cosmetic dissatisfaction was significantly more frequent in the ALR group at the initial follow-up visits compared to the PLTR group. However, this difference was no longer significant at 6 and 12 months follow-up.Conclusion: These data provide strong evidence that ALR is more effective in correction of lower eyelid trachomatous trichiasis with acceptable cosmesis compared with PLTR.Keywords: lower lid, trichiasis, anterior lamellar recession, posterior lamellar tarsal rotation

Javed Ahmad,1,* Sohail Akhter,2,3,* Md Rizwanullah,1 Saima Amin,1 Mahfoozur Rahman,4 Mohammad Zaki Ahmad,5 Moshahid Alam Rizvi,6 Mohammad A Kamal,7 Farhan Jalees Ahmad1,21Department of Pharmaceutics, 2Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India; 3Centre de Biophysique Moléculaire(CBM)-CNRS UPR4301, University of Orléans, Orléans Cedex 2, France; 4Department of Pharmaceutics, Abhilashi College of Pharmacy, Mandi, HP, India; 5Department of Pharmaceutics, College of Pharmacy, Najran University, Saudi Arabia; 6Department of Biosciences, Jamia Millia Islamia, New Delhi, India; 7Metabolomics and Enzymology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia*These authors contributed equally to this workAbstract: Considering the challenges associated with conventional chemotherapy, targeted and local delivery of chemotherapeutics via nanoparticle (NP) carriers to the lungs is an emerging area of interest. Recent studies and growing clinical application in cancer nanotechnology showed the huge potential of NPs as drug carriers in cancer therapy, including in lung carcinoma for diagnosis, imaging, and theranostics. Researchers have confirmed that nanotechnology-based inhalation chemotherapy is viable and more effective than conventional chemotherapy, with lesser side effects. Recently, many nanocarriers have been investigated, including liposomes, polymeric micelles, polymeric NPs, solid lipid NPs, and inorganic NPs for inhalation treatments of lung cancer. Yet, the toxicity of such nanomaterials to the lungs tissues and further distribution to other organs due to systemic absorption on inhalation delivery is a debatable concern. Here, prospect of NPs-based local lung cancer targeting through inhalation route as well as its associated challenges are discussed.Keywords: nanoparticles, lung cancer, inhalational chemotherapy, drug targeting, nanotoxicity

Nasimudeen R Jabir,1 Shams Tabrez,1 Ghulam Md Ashraf,2 Shazi Shakil,3 Ghazi A Damanhouri,4 Mohammad A Kamal11Metabolomics and Enzymology Unit, 2Proteomics and Structural Biology Unit, 3Enzoinformatics Unit, 4Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi ArabiaAbstract: Cancer is a highly complex disease to understand, because it entails multiple cellular physiological systems. The most common cancer treatments are restricted to chemotherapy, radiation and surgery. Moreover, the early recognition and treatment of cancer remains a technological bottleneck. There is an urgent need to develop new and innovative technologies that could help to delineate tumor margins, identify residual tumor cells and micrometastases, and determine whether a tumor has been completely removed or not. Nanotechnology has witnessed significant progress in the past few decades, and its effect is widespread nowadays in every field. Nanoparticles can be modified in numerous ways to prolong circulation, enhance drug localization, increase drug efficacy, and potentially decrease chances of multidrug resistance by the use of nanotechnology. Recently, research in the field of cancer nanotechnology has made remarkable advances. The present review summarizes the application of various nanotechnology-based approaches towards the diagnostics and therapeutics of cancer.Keywords: cancer, diagnosis, drug delivery, nanoparticle, nanotechnology, treatment

BackgroundChildren aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16-week, randomized, placebo-controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4/IL-13 signalling, significantly improved signs and symptoms with acceptable safety; longer-term safety and efficacy data are lacking.ObjectivesTo report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD.MethodsChildren (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study and subsequent open-label extension (OLE) study. Patients received single-dose dupilumab 2 or 4 mg kg-1 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg kg-1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration-time profile and treatment-emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP-NRS) score.ResultsOf 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target-mediated pharmacokinetics characterized dupilumab concentrations (week 24-48 mean serum concentrations: 2 mg kg-1 , 61-77 mg L-1 ; 4 mg kg-1 , 143-181 mg L-1 ). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg-1 , 47%; 4 mg kg-1 , 56%) and AD exacerbation (29% and 13%, respectively). Single-dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP-NRS improved by -37%/-33% and -17%/-20% at week 2 (phase IIa) and -92%/-84% and -70%/-58% at week 52 (OLE), respectively.ConclusionsThese safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years with severe AD.

BackgroundDupilumab (monoclonal antibody inhibiting IL-4/IL-13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate-to-severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16-week, randomised, placebo-controlled phase III trial in adolescents (NCT03054428).ObjectivesTo characterize the pharmacokinetics of dupilumab, and long-term safety and efficacy in adolescents.MethodsThis was a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study with a phase III open-label extension (OLE) in adolescents with moderate-to-severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg-1 or 4 mg kg-1 ) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8-week safety follow-up. Patients then enrolled in the OLE, continuing 2 mg kg-1 or 4 mg kg-1 dupilumab weekly. Primary end points were dupilumab concentration-time profile and incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI).ResultsForty adolescents received dupilumab in the phase IIa study; 36 enrolled in the OLE. Dupilumab showed nonlinear, target-mediated pharmacokinetics. Mean ± SD trough dupilumab concentrations in serum at week 48 (OLE) were 74 ± 19 mg L-1 and 161 ± 60 mg L-1 for 2 mg kg-1 and 4 mg kg-1 , respectively. Dupilumab was well tolerated over 52 weeks; the most common TEAEs were nasopharyngitis (week 52: 41% [2 mg kg-1 ], 47% [4 mg kg-1 ]) and AD exacerbation (29%, 42%). After one dupilumab dose in the phase IIa study, EASI improved from baseline to week 2 [mean ± SD reduction -34% ± 20% (2 mg kg-1 ) and -51% ± 29% (4 mg kg-1 )]. With continuing treatment, EASI scores improved further [week 52: -85% ± 12% (2 mg kg-1 ) and -84% ± 20% (4 mg kg-1 )].ConclusionsIn adolescents with moderate-to-severe AD, dupilumab's pharmacokinetic profile was similar to that in adults. These 52-week safety and efficacy data support long-term use of dupilumab in this patient population. What's already known about this topic? Adolescents with moderate-to-severe atopic dermatitis (AD) have high unmet medical need, with significant disease burden and limited treatment options. Dupilumab (monoclonal antibody against interleukin-4 receptor α) is approved for the treatment of adolescents with moderate-to-severe AD who are inadequately responsive to standard of care (U.S.A.) or candidates for systemic therapy (European Union). A 16-week, randomized, placebo-controlled phase III trial in adolescents demonstrated significant improvements in AD signs/symptoms with an acceptable safety profile. What does this study add? These studies demonstrate the long-term safety and efficacy of dupilumab in adolescents with moderate-to-severe AD for up to 52 weeks of treatment, thus extending and reinforcing the findings from the 16-week dupilumab phase III trial. The data from these studies also support the use of dupilumab in combination with current standard of care (topical corticosteroids), which was not evaluated in the 16-week phase III monotherapy trial.

Abstract Background It is widely recognized that the right ventricle plays a significant role in the prognosis of numerous diseases. However, the assessment of right ventricular function (RV) has not been given much attention until recently. This study used speckle-tracking echocardiography (STE) to assess RV functions in ischemic cardiomyopathy (ICM) patients. Results This study included 74 patients diagnosed with ischemic cardiomyopathy (ICM) and an ejection fraction (EF) of less than 50%. Although all the selected patients had normal RV systolic function by tricuspid annular plane systolic excursion (TAPSE), a considerable percentage of them had subtle RV systolic dysfunction, which could be identified by right ventricular free wall longitudinal strain (RV FWLS) (36.5%) and right ventricular global longitudinal strain (RV GLS) (55.4%). Moreover, the mean RV FWLS was significantly higher than RV GLS (− 20.4 ± 5.08% vs. − 17.5 ± 6.89%), respectively. Advanced left ventricle (LV) adverse remodeling was associated with subtle RV dysfunction. Using multivariate regression analysis, increased E/e' (p = 0.016, CI 1.135–3.423) and RV myocardial performance index (MPI) (p = 0.007, CI 0.000–0.007) were identified as independent factors of impaired RV FWLS with the greatest effectiveness. Conclusion When standard RV measures are normal in patients with ICM, RV systolic strain analysis offers an incremental utility to detect subtle abnormalities in RV function, especially in resource-constrained settings where cardiac magnetic resonance (CMR) is not practical.

Introduction: Breast cancer is a diverse and heterogeneous disease affecting women in both developing and developed countries. In 2022, Global Cancer Observatory (GLOBOCAN) reported 2.3 million cases of breast carcinoma, which accounted for 11.6% of all cancer cases worldwide. The incidence of breast cancer in India has been steadily rising and has surpassed cervical cancer as the most common cancer in women. Invasive ductal carcinoma is the most common histologic type found in all age groups. Grading is done according to Elston Ellis’s modification of the Scarff Bloom Richardson Scoring system. Hormonal {Estrogen Receptor (ER), Progesterone Receptor (PR)} and Human Epidermal growth factor Receptor-2 (HER2/neu) immunohistochemical expression are used for molecular typing of breast carcinoma. Young women account for up to 25% of all breast carcinoma cases in India. Aim: To assess the clinical symptoms, histological type, grade, Immunohistochemistry (IHC) profile (ER, PR, HER2neu), and their relationships in females below 40 years of age with breast carcinoma. Materials and Methods: An ambispective cross-sectional study with a total of 99 cases of breast carcinoma in young females were included in the study, which was conducted in the Department of Pathology at Sri Aurobindo Medical College and PG Institute in Indore, Madhya Pradesh, India, between April 2022 and March 2024. Biopsies, lumpectomy, and total or modified mastectomy specimens were fixed in formalin and paraffin embedded. Sections were stained with Haematoxylin and Eosin (H&E) and IHC markers ER, PR, and HER2neu using Estrogen Receptor Alpha Antibody (EP1), EP2, and EP3 antibodies, respectively, on a fully automated workstation. Carcinomas were classified according to the World Health Organisation (WHO) classification and graded based on Elston Ellis’s modification of the Scarff Bloom Richardson System Scoring. The proportion of tumour cells and intensity were studied, and evaluation was done with appropriate controls. Results: The most common symptom was a breast lump (84.84%), while Invasive breast cancer of {No Special Type (NST)} was the most common histologic type (96.96%) and histological Grade III was predominant (53.53%) in the majority of patients. ER, PR, and HER2neu were positive in 57.57%, 51.51%, and 33.33% of cases, respectively. HER2neu expression was negative in the majority of cases (66.66%). The most common molecular subtype was Luminal A (35.35%), followed by Triple-negative Breast Cancer (TNBC) (29.29%), Luminal B (22.22%), and the least common was the HER2neu enriched subtype (13.13%). Conclusion: Invasive breast carcinoma (NST) is the most common histologic type, with higher histologic grade and a greater number of triple-negative cases seen in young females (

Abstract Background Chronic hypoxia and skeletal muscle atrophy commonly coexist in patients with COPD and CHF, yet the underlying physio‐pathological mechanisms remain elusive. Muscle regeneration, driven by muscle stem cells (MuSCs), holds therapeutic potential for mitigating muscle atrophy. This study endeavours to investigate the influence of chronic hypoxia on muscle regeneration, unravel key molecular mechanisms, and explore potential therapeutic interventions. Methods Experimental mice were exposed to prolonged normobaric hypoxic air (15% pO2, 1 atm, 2 weeks) to establish a chronic hypoxia model. The impact of chronic hypoxia on body composition, muscle mass, muscle strength, and the expression levels of hypoxia‐inducible factors HIF‐1α and HIF‐2α in MuSC was examined. The influence of chronic hypoxia on muscle regeneration, MuSC proliferation, and the recovery of muscle mass and strength following cardiotoxin‐induced injury were assessed. The muscle regeneration capacities under chronic hypoxia were compared between wildtype mice, MuSC‐specific HIF‐2α knockout mice, and mice treated with HIF‐2α inhibitor PT2385, and angiotensin converting enzyme (ACE) inhibitor lisinopril. Transcriptomic analysis was performed to identify hypoxia‐ and HIF‐2α‐dependent molecular mechanisms. Statistical significance was determined using analysis of variance (ANOVA) and Mann–Whitney U tests. Results Chronic hypoxia led to limb muscle atrophy (EDL: 17.7%, P

Abstract Background Evidence synthesis is used by decision-makers in various ways, such as developing evidence-based recommendations for clinical guidelines. Clinical guideline development groups (GDGs) typically discuss evidence synthesis findings in a multidisciplinary group, including patients, healthcare providers, policymakers, etc. A recent mixed methods systematic review (MMSR) identified no gold standard format for optimally presenting evidence synthesis findings to these groups. However, it provided 94 recommendations to help produce more effective summary formats for general evidence syntheses (e.g., systematic reviews). To refine the MMSR recommendations to create more actionable guidance for summary producers, we aimed to explore these 94 recommendations with participants involved in evidence synthesis and guideline development. Methods We conducted a descriptive qualitative study using online focus group workshops in February and March 2023. These groups used a participatory co-design approach with interactive voting activities to identify preferences for a summary format's essential content and style. We created a topic guide focused on recommendations from the MMSR with mixed methods support, ≥ 3 supporting studies, and those prioritized by an expert advisory group via a pragmatic prioritization exercise using the MoSCoW method (Must, Should, Could, and Will not haves). Eligible participants must be/have been involved in GDGs and/or evidence synthesis. Groups were recorded and transcribed. Two independent researchers analyzed transcripts using directed content analysis with 94 pre-defined codes from the MMSR. Results Thirty individuals participated in six focus groups. We coded 79 of the 94 pre-defined codes. Participants suggested a “less is more” structured approach that minimizes methodological steps and statistical data, promoting accessibility to all audiences by judicious use of links to further information in the full report. They emphasized concise, consistently presented formats that highlight key messages, flag readers to indicators of trust in the producers (i.e., logos, websites, and conflict of interest statements), and highlight the certainty of evidence (without extenuating details). Conclusions This study identified guidance based on the preferences of guideline developers and evidence synthesis producers about the format of evidence synthesis summaries to support decision-making. The next steps involve developing and user-testing prototype formats through one-on-one semi-structured interviews to optimize evidence synthesis summaries and support decision-making.

Abstract Background Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient’s likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min. Methods Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort. (2) A post hoc analysis of a subset of trial participants versus a propensity score-weighted contemporaneous comparison group, using external data from the Multicenter Perioperative Outcomes Group (MPOG). The trial included 485 subjects in 11 sites; 406 were in the final effectiveness analysis. The post hoc analysis included 457 trial participants and 15,796 comparison patients. Patients were eligible if aged 18 years or older, American Society of Anesthesiologists (ASA) physical status 3 or 4, and scheduled for moderate- to high-risk noncardiac surgery expected to last at least 3 h. Measurements: minutes of mean arterial pressure (MAP) below 65 mmHg and area under MAP < 65 mmHg. Results Analysis 1: Trial subjects (n = 406) experienced a mean of 9 ± 13 min of MAP below 65 mmHg, compared with the MPOG historical control mean of 25 ± 41 min, a 65% reduction (p < 0.001). Subjects with at least one episode of hypotension (n = 293) had a mean of 12 ± 14 min of MAP below 65 mmHg compared with the MPOG historical control mean of 28 ± 43 min, a 58% reduction (p< 0.001). Analysis 2: In the post hoc inverse probability treatment weighting model, patients in the trial demonstrated a 35% reduction in minutes of hypotension compared to a contemporaneous comparison group [exponentiated coefficient: − 0.35 (95%CI − 0.43, − 0.27); p < 0.001]. Conclusions The use of prediction software for blood pressure management was associated with a clinically meaningful reduction in the duration of intraoperative hypotension. Further studies must investigate whether predictive algorithms to prevent hypotension can reduce adverse outcomes. Trial registration Clinical trial number: NCT03805217. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03805217 . Principal investigator: Xiaodong Bao, MD, PhD. Date of registration: January 15, 2019.

In 2023, a second wave of the global mpox epidemic, which is mainly affecting men who have sex with men (MSM), was observed in some countries. Herein, we benefited from a large viral sequence sampling (76/121; 63%) and vast epidemiological data to characterise the re-emergence and circulation of the Monkeypox virus (MPXV) in Portugal during 2023. We also modelled transmission and forecasted public health scenarios through a compartmental susceptible-exposed-infectious-recovered (SEIR) model. Our results suggest that the 2023 mpox wave in Portugal resulted from limited introduction(s) of MPXV belonging to C.1.1 sublineage, hypothetically from Asia, followed by sustained viral transmission and potential exportation to other countries. We estimated that the contribution of the MSM high sexual activity group to mpox transmission was 120 (95% CrI: 30–3553) times higher than that of the low sexual activity group. However, among the high sexual activity group, vaccinated individuals likely contributed approximately eight times less [0.123 (95% CrI: 0.068–0.208)] than the unvaccinated ones. Vaccination was also linked to potential reduced disease severity, with a Mpox Severity Score of 6.0 in the vaccinated group compared to 7.0 in unvaccinated individuals. Scenario analysis indicated that transmission is highly sensitive to sexual behaviour, projecting that a slight increase in the MSM sub-population with high sexual activity can trigger new mpox waves. This study strongly supports that continued vaccination, targeted awareness among risk groups and routine genomic epidemiology is needed to anticipate and respond to novel MPXV threats (e.g. global dissemination of clade I viruses).

Objectives To quantify the economic investment required to increase bariatric surgery (BaS) capacity in National Health Service (NHS) England considering the growing obesity prevalence and low provision of BaS in England despite its high clinical effectiveness.Design Data were included for the patients with obesity who were eligible for BaS. We used a decision-tree approach including four distinct steps of the patient pathway to capture all associated resource use. We estimated total costs according to the current capacity (current scenario) and three BaS scaling up strategies over a time horizon of 20 years (projected scenario): maximising NHS capacity (strategy 1), maximising NHS and private sector capacity (strategy 2) and adding infrastructure to NHS capacity to cover the entire prevalent and incident obesity populations (strategy 3).Setting BaS centres based in NHS and private sector hospitals in England.Main outcome measures Number of BaS procedures (including revision surgery), cost (GBP) and resource utilisation over 20 years.Results At current capacity, the number of BaS procedures and the total cost over 20 years were estimated to be 140 220 and £1.4 billion, respectively. For strategy 1, these values were projected to increase to 157 760 and £1.7 billion, respectively. For strategy 2, the values were projected to increase to 232 760 and £2.5 billion, respectively. Strategy 3 showed the highest increase to 564 784 and £6.4 billion, respectively, with an additional 4081 personnel and 49 facilities required over 20 years.Conclusions The expansion of BaS capacity in England beyond a small proportion of the eligible population will likely be challenging given the significant upfront economic investment and additional requirement of personnel and infrastructure.

Abstract Metabolic and bariatric surgery (MBS) is widely considered the most effective option for treating obesity, a chronic, relapsing, and progressive disease. Recently, the American Society of Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) issued new guidelines on the indications for MBS, which have superseded the previous 1991 National Institutes of Health guidelines. The aim of this study is to establish the first set of consensus guidelines for selecting procedures in Class I and II obesity, using an Expert Modified Delphi Method. In this study, 78 experienced bariatric surgeons from 32 countries participated in a two-round Modified Delphi consensus voting process. The threshold for consensus was set at an agreement or disagreement of ≥ 70.0% among the experts. The experts reached a consensus on 54 statements. The committee of experts reached a consensus that MBS is a cost-effective treatment option for Class II obesity and for patients with Class I obesity who have not achieved significant weight loss through non-surgical methods. MBS was also considered suitable for patients with Type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 30 kg/m2 or higher. The committee identified intra-gastric balloon (IGB) as a treatment option for patients with class I obesity and endoscopic sleeve gastroplasty (ESG) as an option for patients with class I and II obesity, as well as for patients with T2DM and a BMI of ≥ 30 kg/m2. Sleeve gastrectomy (1) and Roux-en-Y gastric bypass (RYGB) were also recognized as viable treatment options for these patient groups. The committee also agreed that one anastomosis gastric bypass (OAGB) is a suitable option for patients with Class II obesity and T2DM, regardless of the presence or severity of obesity-related medical problems. The recommendations for selecting procedures in Class I and II obesity, developed through an Expert Modified Delphi Consensus, suggest that the use of standard primary bariatric endoscopic (IGB, ESG) and surgical procedures (SG, RYGB, OAGB) are acceptable in these patient groups, as consensus was reached regarding these procedures. However, randomized controlled trials are still needed in Class I and II Obesity to identify the best treatment approach for these patients in the future.

Abstract Corneal HSV-1 infections are a leading cause of infectious blindness globally by triggering tissue damage due to the intense inflammation. HSV-1 infections are treated mainly with antiviral drugs that clear the infections but are inefficient as prophylactics. The body produces innate cationic host defence peptides (cHDP), such as the cathelicidin LL37. Various epithelia, including the corneal epithelium, express LL37. cHDPs can cause disintegration of pathogen membranes, stimulate chemokine production, and attract immune cells. Here, we selected GF17, a peptide containing the LL37 fragment with bioactivity but with minimal cytotoxicity, and added two cell-penetrating amino acids to enhance its activity. The resulting GF19 was relatively cell-friendly, inducing only partial activation of antigen presenting immune cells in vitro. We showed that HSV-1 spreads by tunneling nanotubes in cultured human corneal epithelial cells. GF19 given before infection was able to block infection, most likely by blocking viral entry. When cells were sequentially exposed to viruses and GF19, the infection was attenuated but not arrested, supporting the contention that the GF19 mode of action was to block viral entry. Encapsulation into silica nanoparticles allowed a more sustained release of GF19, enhancing its activity. GF19 is most likely suitable as a prevention rather than a virucidal treatment.

This study concerns the effect of the external prestressing strand shape profile on the flexural behavior of steel beams. Seven steel beams that have the same cross-section are strengthened by external strands fixed by using Saddle Points of Deviation (Deviators). Based on two criteria, beams tested are divided into two categories whether external prestressing with fixity strands is present. The first group includes only one beam as a reference, while the second group deals with beams strengthened by two external strands. Six samples have been separated according to the eccentricity for external prestressing at a jacking stress of 815 MPa. During testing, it was discovered that the moment-curvature responses at the bottom and top flange region were stiffer than those in the reference, and the degree of hardening increases with eccentricity increasing. However, failure occurs with a slight warning as a result of insufficient ductility. Due to the presence of external prestressing, the ultimate moment capacity is enhanced by approximately 6.1%, 31.7%, 38.5%, 57.6%, 29.4%, and 80.2% as compared to the reference. Finally, the radius of curvature at the top flange region for strengthening samples has grown by approximately -16.7%, 8.0%, -26.9%, 21.5%, 17.5%, and 17.4% as compared to the reference case. In contrast, the percentage of the radius of curvature at the bottom flange region for strengthened samples dropped to 24,9%, 73.9%, 83.2%, 83.6%, 69.2%, and 89.0%, respectively, with an increase in the eccentricity position as compared to the reference.

Abstract Background Endobronchial forceps are commonly used for complex IVC filter removal and after initial attempts at IVC filter retrieval with a snare have failed. Currently, there are no clear guidelines to help distinguish cases where primary removal should be attempted with standard snare technique or whether attempts at removal should directly be started with forceps. This study is aimed to identify clinical and imaging predictors of snare failure which necessitate conversion to endobronchial forceps. Methods Retrospective analysis of 543 patients who underwent IVC filter retrievals were performed at three large quaternary care centers from Jan 2015 to Jan 2022. Patient demographics and IVC filter characteristics on cross-sectional images (degree of tilt, hook embedment, and strut penetration, etc.) were reviewed. Binary multivariate logistic regression was used to identify predictors of IVC filter retrieval where snare retrieval would fail. Results Thirty seven percent of the patients (n = 203) necessitated utilization of endobronchial forceps. IVC filter hook embedment (OR:4.55; 95%CI: 1.74–11.87; p = 0.002) and strut penetration (OR: 56.46; 95% CI 20.2–157.7; p = 0.001) were predictors of snare failure. In contrast, total dwell time, BMI, and degree of filter tilt were not associated with snare failure. Intraprocedural conversion from snare to endobronchial forceps was significantly associated with increased contrast volume, radiation dose, and total procedure times (p

Introduction: Sexually transmitted infections (STIs) continue to occur at high levels. According to the WHO, each year there are an estimated 374 million new infections with syphilis, gonorrhea, chlamydia, and trichomoniasis. STIs are associated with an increased risk of acquiring HIV infection. Migrants are reportedly highly affected by STIs. Objectives: This study aims to characterize factors associated with STIs in a population of HIV-positive migrants living in Portugal. Methodology: This is a cross-sectional observational study of 265 newly diagnosed HIV-1 positive migrants, who were defined as individuals born outside Portugal. This group of people were part of the BESTHOPE study that was developed in 17 Portuguese hospitals between September 2014 and December 2019, and included information collected through sociodemographic and behavioral questionnaires filled in by the migrant patients, clinical questionnaires filled in by the clinicians and HIV-1 genomic sequences generated through resistance testing (Sanger sequencing). A multivariable statistical analysis was used to analyze the association between sociodemographic characteristics, sexual behaviors, HIV testing and sexual infections. Results: Most HIV-1 positive individuals included in the study were men (66.8%) and aged between 25 and 44 years old (59.9%). Men had a higher proportion of STIs when compared to women (40.4% vs. 14.0%) and the majority of men reported homosexual contacts (52.0%). Most men reported having had two or more occasional sexual partners in the previous year (88.8%) and 50.9% reported always using condoms with occasional partners, while 13.2% never used it. For regular partners, only 29.5% of the women reported using condoms, compared to 47.3% of men. Other risk behaviors for acquiring HIV, such as tattooing and performing invasive medical procedures, were more prevalent in men (38.0% and 46.2%, respectively), when compared to women (30.4% and 45.1% respectively) and 4.7% of men reported having already shared injectable materials, with no data for comparison in the case for women. Additionally, 23.9% of women reported having had a blood transfusion while only 10.3% of men reported having had this medical procedure. Meanwhile, 30.9% of the individuals reported having been diagnosed with some type of STI in the last 12 months. In addition, 43.3% of individuals that answered a question about hepatitis reported to be infected with hepatitis B, while 13.0% reported having hepatitis C infection. According to the multivariable analysis, the only transmission route was significantly associated with reports of previous STI infection: men who have sex with men (MSM) were 70% more likely to have been diagnosed with an STI in the past 12 months compared to the heterosexual route. Conclusion: HIV-1 infected men were more likely to report previous STIs than women. On the other hand, most migrant women had a regular sexual partner and never or only sometimes used condoms. This somewhat discrepant findings suggest that gender inequalities may make women unable to negotiate safe sexual practices, resulting in increased susceptibility to infection. However, since migrant women report less STIs, we cannot exclude that these STIs may remain undiagnosed. The implementation of safer sex awareness campaigns for condom use and screening for STIs in women is crucial. On the other hand, health education campaigns for STI knowledge need to be implemented for both MSM and women and their partners.

Abstract Background In the UK, bariatric surgical patients are followed up for 2 years post‐operatively in hospital settings, before being discharged into General Practice for long‐term follow‐up. Presently, there is ambiguous guidance as to what should be included in a community‐based bariatric surgical follow‐up service. The aim of the study was to understand, from both patient and professional perspectives, what is needed to support the long‐term management of bariatric surgical patients in community‐based settings. Methods Post‐surgical bariatric patients and General Practice staff were recruited from an area in the UK which has an National Health Service (NHS) hospital providing a high‐volume and established bariatric surgical service. Data was collected through semi‐structured interviews. A thematic analytic framework was used to construct eight themes which illuminated the participants' experiences. The study took place between March and December 2021. Findings Thirty participants (14 patients and 16 healthcare professionals) were recruited to the study. The study revealed the lack of a framework for delivery of a long‐term follow up service was frustrating to both patients and professionals. Patient participants reported needing more support, especially dietetic and psychological input, and professionals stated they had little knowledge about bariatric surgical care, and what was needed to provide optimal care, but wanted to provide quality patient care. Conclusion Long‐term follow up of bariatric surgical patients is an important issue which needs addressing. This study illuminates both the patient and professional perspectives on developing a pragmatic, community‐based service which meets the needs of patients and considers the need to incorporate such a service into existing infrastructures without adding additional demands on General Practice.

Abstract Background The first year of the Covid‐19 pandemic saw drastic changes to bariatric surgical practice, including postponement of procedures, altered patient care and impacting on the role of bariatric surgeons. The consequences of this both personally and professionally amongst bariatric surgeons has not as yet been explored. Aims The aim of this research was to understand bariatric surgeons' perspectives of working during the first year of the pandemic to explore the self‐reported personal and professional impact. Methods Using a retrospective, two phased, study design with global participants recruited from closed, bariatric surgical units. The first phase used a qualitative thematic analytic framework to identify salient areas of importance to surgeons. Themes informed the construction of an on‐line, confidential survey to test the potential generalizability of the interview findings with a larger representative population from the global bariatric surgical community. Findings Findings of the study revealed that the first year of the pandemic had a detrimental effect on bariatric surgeons both personally and professionally globally. Conclusion This study has identified the need to build resilience of bariatric surgeons so that the practice of self‐care and the encouragement of help‐seeking behaviors can potentially be normalized, which will in turn increase levels of mental health and wellbeing.

Abstract Little is known about electrocardiogram (ECG) markers of Parkinson’s disease (PD) during the prodromal stage. The aim of the study was to build a generalizable ECG-based fully automatic artificial intelligence (AI) model to predict PD risk during the prodromal stage, up to 5 years before disease diagnosis. This case–control study included samples from Loyola University Chicago (LUC) and University of Tennessee-Methodist Le Bonheur Healthcare (MLH). Cases and controls were matched according to specific characteristics (date, age, sex and race). Clinical data were available from May, 2014 onward at LUC and from January, 2015 onward at MLH, while the ECG data were available as early as 1990 in both institutes. PD was denoted by at least two primary diagnostic codes (ICD9 332.0; ICD10 G20) at least 30 days apart. PD incidence date was defined as the earliest of first PD diagnostic code or PD-related medication prescription. ECGs obtained at least 6 months before PD incidence date were modeled to predict a subsequent diagnosis of PD within three time windows: 6 months–1 year, 6 months–3 years, and 6 months–5 years. We applied a novel deep neural network using standard 10-s 12-lead ECGs to predict PD risk at the prodromal phase. This model was compared to multiple feature engineering-based models. Subgroup analyses for sex, race and age were also performed. Our primary prediction model was a one-dimensional convolutional neural network (1D-CNN) that was built using 131 cases and 1058 controls from MLH, and externally validated on 29 cases and 165 controls from LUC. The model was trained on 90% of the MLH data, internally validated on the remaining 10% and externally validated on LUC data. The best performing model resulted in an external validation AUC of 0.67 when predicting future PD at any time between 6 months and 5 years after the ECG. Accuracy increased when restricted to ECGs obtained within 6 months to 3 years before PD diagnosis (AUC 0.69) and was highest when predicting future PD within 6 months to 1 year (AUC 0.74). The 1D-CNN model based on raw ECG data outperformed multiple models built using more standard ECG feature engineering approaches. These results demonstrate that a predictive model developed in one cohort using only raw 10-s ECGs can effectively classify individuals with prodromal PD in an independent cohort, particularly closer to disease diagnosis. Standard ECGs may help identify individuals with prodromal PD for cost-effective population-level early detection and inclusion in disease-modifying therapeutic trials.

IntroductionHIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019.MethodsWe included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP).ResultsThe median age was 31 years, 51% had a current income between 501–1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP.ConclusionOur study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

Introdução: A Organização Mundial de Saúde e a comunidade médica têm vindo a reconhecer a necessidade de intervir nos grupos considerados como minorias sexuais e de género, nomeadamente na comunidade de lésbicas, gays, bissexuais, “trans” (transgéneros e transsexuais), queer e intersexuais (LGBTQI). Objetivos: O presente artigo pretende rever a terminologia utilizada na distinção dos vários grupos de orientação sexual, identidade de género, outros conceitos relevantes e o seu impacto clínico. Materiais e métodos: Revisão da literatura com recurso à base de dados científica Pubmed utilizando as palavras-chave gender identity, gender variance, transgender, sexual orientation, transsexualism. Foi realizada pesquisa da terminologia e conceitos LGBTQI em websites e jornais de associações de apoio à comunidade LGBTQI. Resultados: A identidade de género é a forma como uma pessoa se identifica internamente e que determina a expressão de género, a qual resulta da combinação do comportamento, linguagem, apresentação estética e contexto cultural. A orientação sexual corresponde à atração sexual e/ou emocional que pode contribuir para o estabelecimento de relações sexuais e/ou emocionais e é determinada por três dimensões: a atração, o comportamento e a identidade sexual. Discussão: Alguns estudos mostram que utentes LGBTQI podem ter uma menor procura de cuidados de saúde, em particular devido ao receio de discriminação. Estes apresentam também necessidades específicas em cuidados de saúde, conforme os fatores de risco de exposição sexual ou inerentes à redesignação sexual cirúrgica/médica. Conclusão: O género e a sexualidade são determinantes sociais para a saúde que devem ser distinguidos e aferidos na prestação de cuidados de saúde. O clínico deve estar sensibilizado para reconhecer esses problemas e intervir.

The Indian River Lagoon System (IRLS) has been impacted by the surrounding development, leading to excessive nutrient loads that have resulted in frequent and prolonged phytoplankton blooms in the northern reaches. Our study focused on estimating terrestrial groundwater discharge (TGD) and associated nutrient loads by combining field measurements and hydrogeologic modeling at four transects: Eau Gallie (EGT), River Walk (RWT), Banana River (BRT), and Mosquito Lagoon (MLT) across the IRLS. Multiple monitoring stations were installed to collect groundwater and surface water levels, salinity, and nutrient concentrations during 2014-2015. Samples were analyzed for dissolved inorganic nitrogen (DIN) and dissolved inorganic phosphorus (DIP). Numerical modeling was accomplished using SEAWAT to simulate TGD rates, whereas nutrient loads were calculated by multiplying simulated TGD by measured concentrations. TGD rates and nutrient loads were also estimated specifically for the “near-shore zone” along each transect. The effect of recharge from underlying Hawthorn Formation was also evaluated by incorporating estimated recharge rates into the models. Porewater and lagoon water samples showed that ammonium predominated over (NO2+NO3) and PO4 at all sites, resulting in DIN/DIP ratio surpassing the Redfield ratio. Low nitrite/nitrate, coupled with elevated ammonium concentrations at RWT, BRT, and MLT, may be attributed to biogeochemical transformations catalyzed by mangroves and wetlands. Simulated TGD showed mild temporal but significant spatial variation, especially between EGT and RWT compared to BRT and MLT. The highest average TGD of 0.73 and 0.77 m3/d.m occurred at RWT and EGT, respectively, whereas the lowest rates were predicted at BRT and MLT. The highest estimated average DIN loads of 507 and 428 g/yr.m were received at EGT and RWT, respectively, whereas MLT and BRT exhibited lower loads. The DIP loads were remarkably lower than the DIN loads and were significantly different in space and time between sites. Elevated DIN combined with reduced DIP resulted in DIN/DIP exceeding the Redfield ratio, thereby encouraging the blooming of harmful algae. Although the majority of seepage occurs through the near-shore zone, small amounts are received along the entire transect at all sites. The Hawthorn Formation does not contribute significant recharge to the aquifer at the transect locations.

Abstract Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2. Remdesivir (RDV) and corticosteroids are used mainly in COVID-19 patients with acute respiratory failure. The main objective of the study was to assess the effectiveness of remdesivir with and without corticosteroids in the treatment of COVID-19 patients. We conducted a prospective observational study, including adult patients consecutively hospitalized with confirmed COVID-19 and acute respiratory failure. Patients were divided according to treatment strategy: RDV alone versus RDV with corticosteroids. The primary outcome was the time to recovery in both treatment groups. We included 374 COVID-19 adult patients, 184 were treated with RDV, and 190 were treated with RDV and corticosteroid. Patients in the RDV group had a shorter time to recovery in comparison with patients in the RDV plus corticosteroids group at 28 days after admission [11 vs. 16 days (95% confidence Interval 9.7–12.8; 14.9–17.1; p = .016)]. Patients treated with RDV alone had a shorter length of hospital stay. The use of corticosteroids as adjunctive therapy of RDV was not associated with improvement in mortality of COVID-19 patients.

The recent technological advances allowed us to produce some new wearable devices, such as smartphones and smartwatches (SW). These devices provide different services to their users through different software applications installed even in the SW or smartphones. Health monitoring functionalities, among these services, are nowadays the new technological fashion. In fact, the monitoring is ensured by the sensor incorporated in the SW. The SW allows the record of only one single lead Electrocardiogram (ECG), which is sufficient to screen or diagnosis of rhythm and conduction disorders, especially during the onset of cardiac symptoms, but insufficient for the detection of ischemic disease and cardiomyopathies. In this context, this paper aims to evaluate the feasibility, and reliability of a SW to obtain ECG recordings in comparison with a standard ECG. For that purpose, 140 patients were recruited for this analysis. At the first step, the 12 lead ECG followed with four lead SW-ECG; using the Withings Scanwatch device, were recorded in the same resting conditions. The four lead SW-ECG consists of Einthoven DI lead recorded with the SW, where the SW was on the left wrist and the right index finger on the crown, and three Wilson-type leads, in the which the V1 was recorded in the fourth right parasternal intercostal space, V3 was recorded in the fifth intercostal space on the midclavicular line, and V6 was recorded in the fifth intercostal space on the left midaxillary line with the right index finger placed on the crown and the left hand encompassing the right wrist. 700 ECGs recordings were collected and statistically analyzed in this study. In total, 97 % of the patients were able to obtain an ECG through the SW. A strong correlation was observed between the two recording methods concerning the duration of the studied parameters (r >90 %). The correlation coefficient showed that 33 out of 44 parameters have a strong correlation with the standard ECG. The similarity of the combined leads in the 4 established subgroups was significantly higher, meaning that increasing the number of leads would improve the detection of electrical anomalies. Our findings confirm the existing data on the high similarity between SW and standard 12-leads ECG. Despite SW not having the accuracy and utility of the standard ECG machine, they should be considered as an interesting screening tool for cardiac rhythm disorders, and a compelling solution to electrical documentation of general cardiac symptoms.

Introduction: The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) framework provides a structured and transparent approach for clinical guideline developers to use when formulating recommendations. Understanding how stakeholders use the EtD framework will inform how best to provide future training and support. This scoping review objective is to identify the key characteristics of how the GRADE EtD framework is used and identify studies on perception of use by those involved in developing clinical guidelines. Methods: JBI methodology for scoping reviews will be followed. This scoping review will consider both peer review published literature and grey literature. This will include empirical studies on the use of EtDs (including both quantitative, qualitative, and mixed methods primary research articles) and discussion papers/ commentaries on the experience of using the EtD. It will also include a random sample of publicly available populated EtDs identified from databases and repositories of GRADE guidelines. The search strategy will aim to locate both published and unpublished documents. First, we will conduct an exploratory search of MEDLINE and Embase (Elsevier), supplemented with citation analysis of included articles. Populated EtDs will be identified through searches of databases and repositories of GRADE guidelines. Two researchers will independently screen, select, and extract identified documents. Data will be presented in tables and summarized descriptively. Conclusion: This scoping review will identify the key characteristics of how the GRADE EtD framework is currently being used in clinical guidelines. Review findings can be used to inform future guidance and requirements for using GRADE EtD, as well as training on how to consider the criteria in developing recommendations. Results will be disseminated through publications in peer – reviewed journals and conference presentations. We will present our findings to relevant stakeholders via the networks of the co-author team at a one-day workshop.

Abstract Background Intensivists target different blood pressure component values to manage intensive care unit (ICU) patients with sepsis. We aimed to evaluate the relationship between individual blood pressure components and organ dysfunction in critically ill septic patients. Methods In this retrospective observational study, we evaluated 77,328 septic patients in 364 ICUs in the eICU Research Institute database. Primary exposure was the lowest cumulative value of each component; mean, systolic, diastolic, and pulse pressure, sustained for at least 120 min during ICU stay. Primary outcome was ICU mortality and secondary outcomes were composite outcomes of acute kidney injury or death and myocardial injury or death during ICU stay. Multivariable logistic regression spline and threshold regression adjusting for potential confounders were conducted to evaluate associations between exposures and outcomes. Sensitivity analysis was conducted in 4211 patients with septic shock. Results Lower values of all blood pressures components were associated with a higher risk of ICU mortality. Estimated change-points for the risk of ICU mortality were 69 mmHg for mean, 100 mmHg for systolic, 60 mmHg for diastolic, and 57 mmHg for pulse pressure. The strength of association between blood pressure components and ICU mortality as determined by slopes of threshold regression were mean (− 0.13), systolic (− 0.11), diastolic (− 0.09), and pulse pressure (− 0.05). Equivalent non-linear associations between blood pressure components and ICU mortality were confirmed in septic shock patients. We observed a similar relationship between blood pressure components and secondary outcomes. Conclusion Blood pressure component association with ICU mortality is the strongest for mean followed by systolic, diastolic, and weakest for pulse pressure. Critical care teams should continue to follow MAP-based resuscitation, though exploratory analysis focusing on blood pressure components in different sepsis phenotypes in critically ill ICU patients is needed.

Introduction: A bone marrow examination involves the pathological analysis of samples from the bone marrow, which are obtained through bone marrow aspiration (BMA) and biopsy procedures. This examination is employed for the diagnosis of various hematological and nonhematological conditions. Both aspirate and biopsy samples are essential, offering a comprehensive bone marrow assessment. Objectives: In this study, we aim to compare the simultaneous evaluation of bone marrow aspirates and biopsies and to study diagnostic accuracy and concordance rate. Materials and Methods: This research was performed at the Department of Pathology, Shri Aurobindo Medical College, and Postgraduate Institute in Indore, Madhya Pradesh, India. The study was conducted from January 2019 to December 2019 and evaluated 200 patients. In 170 instances, bone marrow biopsy (BMB) and BMA procedures were conducted simultaneously, with 14 cases excluded due to issues like hemodilution or inadequate samples. Microscopic examinations were carried out on both aspirate slides and trephine biopsy sections, with the findings meticulously documented. Results: In the present research, the most prevalent clinical reason for performing a bone marrow examination was anemia (28.2%), closely followed by acute leukemias (21.9%). Among the 156 cases examined, BMA and biopsy led to a definitive diagnosis in 116 patients (74.3%), while biopsy alone diagnosed 27 cases (17.3%). Conclusion: While BMB continues to be the established benchmark for bone marrow analysis due to its heightened reliability and sensitivity, the combined use of both BMA and BMB enhances diagnostic yield significantly.

Beta thalassemia is an inherited disorder resulting in abnormal or decreased production of hemoglobin, leading to hemolysis and chronic anemia. The long-term complications can affect multiple organ systems, namely the liver, heart, and endocrine. Myocardial iron overload is a common finding in β-thalassemia. As a result, different cardiovascular complications in the form of cardiomyopathy, pulmonary hypertension, arrhythmias, and vasculopathies can occur, and in extreme cases, sudden cardiac death. Each of these complications pertains to underlying etiologies and risk factors, which highlights the importance of early diagnosis and prevention. In this review, we will discuss different types of cardiovascular complications that can manifest in patients with β-thalassemia, in addition to the current diagnostic modalities, preventive and treatment modalities for these complications.

Self-driving cars are going to be the main future mode of transportation. However, such systems like, any other cyber-physical system, are vulnerable to attack vectors and uncertainties. As a response, resilience-based approaches are being developed. However, the approaches lack a sound attack model that recognizes the attack vectors and vulnerabilities such a system would have and that does a proper severity analysis of such attacks. Moreover, the existing attack models are too generic. Currently, the domain lacks such specific work pertaining to self-driving cars. Given the technology and architecture of self-driving cars, the field requires a domain-specific attack model. This paper gives a review of the attack models and proposes a domain-specific attack model for self-driving cars. The proposed attack model, severity-based analytical attack model for resilience (SAAMR), provides attack analysis based on existing models. Also, a domain-based severity score for attacks is calculated. Further, the attacks are classified using the decision-tree method and predictions of the type of attacks are given using long short-term memory network.

Abstract Introduction Obesity is a known risk factor for the development of cancers, and a significant proportion of the population may be at risk of developing cancer owing to their weight status. There is acknowledged societal stigma towards people living with obesity, which can influence health behaviors and deter help seeking, such as cancer screening. Healthcare professionals’ attitudes and views toward people living with obesity may adversely affect the patient–professional interface and treatment. Methods A systematic review was carried out which aimed to explore the impact of living with obesity on the uptake of three main cancer‐screening services: breast, cervical, and colorectal. Results Ten studies were included in the review. Three main areas were identified from both a patient and healthcare professional perspective: barriers and challenges to screening, gender issues, and disparities in the population living with obesity. Conclusion Further research is needed to improve uptake of cancer screening services, and for education on weight bias, which is often unconscious, to be considered for healthcare professionals working in cancer screening services. This may help to increase the incidence of early differential diagnosis of potential cancers and improve health outcomes for people living with obesity.

Abstract Coronavirus disease 2019 (COVID‐19) is associated with endothelial dysfunction. Pharmacologically targeting the different mechanisms of endothelial dysfunction may improve clinical outcomes and lead to reduced morbidity and mortality. In this pilot, double‐blind, placebo‐controlled, randomized clinical trial, we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID‐19 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L‐arginine, folate, Nebivolol, and atorvastatin) or placebo for up to 14 days. The primary outcome was time to recovery, measured by an eight category ordinal scale and defined by the time to being discharged from the hospital or hospitalized for infection‐control or other nonmedical reasons. Secondary outcomes included the composite outcome of intensive care unit (ICU) admission or the need for mechanical ventilation, all‐cause mortality, and the occurrence of side effects. Of 42 randomized patients, 37 were included in the primary analysis. The mean age of the patients was 57 years; the mean body mass index of study participants was 29.14. History of hypertension was present in 27% of the patients, obesity in 45%, and diabetes mellitus in 21.6%. The median (interquartile range) time to recovery was not significantly different between the endothelial protocol group (6 [4–12] days) and the placebo group (6 [5–8] days; p value = 0.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all‐cause mortality, or the occurrence of side effects between the endothelial protocol group and the placebo group. Among patients hospitalized with mild, moderate, or severe COVID‐19 infection, targeting endothelial dysfunction by administering Nicorandil, L‐arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. Based on this study’s findings, targeting endothelial dysfunction did not result in a clinically significant improvement in outcome and, as such, larger trials targeting this pathway are not recommended.

Abstract Background Patients presenting with acute abdominal pain that occurs after months or years following bariatric surgery may present for assessment and management in the local emergency units. Due to the large variety of surgical bariatric techniques, emergency surgeons have to be aware of the main functional outcomes and long-term surgical complications following the most performed bariatric surgical procedures. The purpose of these evidence-based guidelines is to present a consensus position from members of the WSES in collaboration with IFSO bariatric experienced surgeons, on the management of acute abdomen after bariatric surgery focusing on long-term complications in patients who have undergone laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Method A working group of experienced general, acute care, and bariatric surgeons was created to carry out a systematic review of the literature following the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) and to answer the PICO questions formulated after the Operative management in bariatric acute abdomen survey. The literature search was limited to late/long-term complications following laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Conclusions The acute abdomen after bariatric surgery is a common cause of admission in emergency departments. Knowledge of the most common late/long-term complications (> 4 weeks after surgical procedure) following sleeve gastrectomy and Roux-en-Y gastric bypass and their anatomy leads to a focused management in the emergency setting with good outcomes and decreased morbidity and mortality rates. A close collaboration between emergency surgeons, radiologists, endoscopists, and anesthesiologists is mandatory in the management of this group of patients in the emergency setting.

Background: Postoperative acute kidney injury (AKI) is a common complication and is associated with increased hospital length of stay and 30 day all-cause mortality. Unfortunately, we have neither a defined strategy to prevent AKI nor an effective treatment. In vitro, animal, and human studies have suggested that dexmedetomidine may have a renoprotective effect. We conducted a retrospective cohort study to evaluate if intraoperative dexmedetomidine was associated with a reduced incidence of AKI. Methods: We collected data from 6625 patients who underwent major non-cardiothoracic cancer surgery. Before and after propensity score matching, we compared the incidence of postoperative AKI in patients who received intraoperative dexmedetomidine and those who did not. AKI was defined according to the Kidney Disease Improving Global Outcomes (creatinine alone values) criteria and calculated for postoperative Days 1, 2, and 3. Results: Twenty per cent (n=1301) of the patients received dexmedetomidine. The mean [standard deviation] administered dose was 78 [49.4] mcg. Patients treated with dexmedetomidine were matched to those who did not receive the drug. Patients receiving dexmedetomidine had a longer anaesthesia duration than the non-dexmedetomidine group. The incidence of AKI was not significantly different between the groups (dexmedetomidine 8% vs no dexmedetomidine 7%; P=0.333). The 30 day rates of infection, cardiovascular complications, or reoperation attributable to bleeding were higher in patients treated with dexmedetomidine. The 30 day mortality rate was not statistically different between the groups. Conclusions: The administration of dexmedetomidine during major non-cardiothoracic cancer surgery is not associated with a reduction in AKI within 72 h after surgery.

Abstract Background Inferior vena cava (IVC) filter retrieval is typically accomplished with standard snare technique. When this fails, more advanced techniques are necessary, especially when removal falls outside a 12-month window. Complications during filter retrieval depend heavily on technique, type of filter, and filter position. In this study we examined safety and efficacy of 536 filter retrievals at a tertiary care center and compared complication rates between standard snare and endobronchial forcep retrieval. Method We reviewed 536 cases between August 2015 and August 2020, recording retrieval success rates, patient comorbidities, and complication rates at the time of removal. Results Total overall retrieval success was 97.9% (525/536), and complications occurred in approximately 6.0% (32/536) of all cases. Success and complications with standard snare technique alone were 99.4% (345/347) and 1.7% (5 Grade I/II, 1 Grade III) and advanced forcep technique 98.8% (171/173) and 14.5% (22 Grade I/II, 2 Grade III, and 1 Grade IV), respectively. There was no significant difference between the technical success rates of the standard snare technique and forceps techniques (p = 0.60) despite a significantly longer dwell time in patients undergoing forceps retrieval (p

Background Prostate cancer (PCa) is the second most frequent malignancy (after lung cancer) in men worldwide .In prostate cancer, immunohistochemistry (IHC) has an important role in the diagnostic confirmation. Gleason score, tumour volume, surgical margins and Ki-67 index are the most significant prognostic factors. The value of different biomarkers like p53, Ki-67, PSMA, androgen receptor mutations, IGF, E-cadherin remains to be applied in clinical practice. In the present study we studied the expression of PSMA and Ki 67 IHC marker in prostatic carcinoma cases and its relation with Gleason score and Gleason grade group of tumour. Method A total of 52 cases of prostate carcinoma diagnosed on histopathology as adenocarcinoma in the Department of surgical pathology within 2.5 years duration were further studied immunohistochemically by PSMA and Ki 67 antibodies. Results At the time of presentation most of the cases have serum PSA level 11-50 ng/ml and with increasing Gleason score it can be ≥100ng/ml. Majority of cases have Gleason score 7 and the most common Gleason grade group is 2. PSMA and Ki 67 IHC marker is significantly correlated with Gleason score and Gleason grade group. PSMA expression is significantly correlated with perineural invasion and Ki 67 with bone metastasis. Conclusion PSMA and Ki 67 IHC marker can be used in conjunction with or as a substitute to Gleason scoring system for proper risk.