Portal vein thrombosis after laparoscopic splenectomy: an ongoing clinical challenge.

ObjectivesPortal vein thrombosis (PVT) following open splenectomy is a potentially lethal complication with an incidence of up to 6%. The objective of this report is to describe our management of a recent laparoscopic case, discuss current therapies, and consider antiplatelet therapy for prophylaxis.MethodsMedical records, laboratory studies, and imaging studies pertaining to a recent case of a laparoscopic splenectomy were examined. Current literature related to this topic was reviewed.ResultsA 16-year-old girl underwent laparoscopic splenectomy for idiopathic thrombocytopenic purpura. Her preoperative platelet count was 96K. She was discharged on postoperative day 1 after an uneventful operation including division of the splenic hilum with an endoscopic linear stapler. On postoperative day 20, she presented with a 5-day history of epigastric pain, nausea, and low-grade fevers without peritoneal signs. Her white blood cell count was 17.3; her platelets were 476K. Computed tomography demonstrated thrombosis of the splenic, superior mesenteric, and portal veins propagating into the liver. Heparinization was begun followed by an unsuccessful attempt at pharmacologic and mechanical thrombolysis by interventional radiology. Over the next 5 days, her pain resolved, she tolerated a full diet, was converted to oral anticoagulation and sent home. Follow-up radiographic studies demonstrated the development of venous collaterals and cavernous transformation of the portal vein.DiscussionNo standard therapy for PVT exists; several approaches have been described. These include systemic anticoagulation, systemic or regional medical thrombolysis, mechanical thrombolysis, and surgical thrombectomy. Unanswered questions exist about the most effective acute therapy, duration of anticoagulation, and the potential efficacy of routine prophylaxis with perioperative antiplatelet agents. PVT following splenectomy occurs with both the open and laparoscopic approach

Modeling Approaches for Addressing Simple Unrelaxable Constraints with Unconstrained Optimization Methods

We explore novel approaches for solving nonlinear optimization problems with unrelaxable bound constraints, which must be satisfied before the objective function can be evaluated. Our method reformulates the unrelaxable bound-constrained problem as an unconstrained optimization problem that is amenable to existing unconstrained optimization methods. The reformulation relies on a domain warping to form a merit function; the choice of the warping determines the level of exactness with which the unconstrained problem can be used to find solutions to the bound-constrained problem, as well as key properties of the unconstrained formulation such as smoothness. We develop theory when the domain warping is a multioutput sigmoidal warping, and we explore the practical elements of applying unconstrained optimization methods to the formulation. We develop an algorithm that exploits the structure of the sigmoidal warping to guarantee that unconstrained optimization algorithms applied to the merit function will find a stationary point to the desired tolerance.Comment: 20 pages, 5 figure

The African snakebite Alliance

The goal to reduce the burden of snakebite envenoming is challenged by the gaps in evidence for clinical care and public health. These evidence gaps and the absence of a strong network are illustrated by bibliometrics. The African Snakebite Alliance is a multidisciplinary group focusing on research themes which will generate evidence needed to shape policy and practice

Stakeholder perspectives from 15 countries in Africa on barriers in snakebite envenoming research and the potential role of research hubs

Snakebite envenoming is a debilitating neglected tropical disease disproportionately affecting the rural poor in low and middle-income countries in the tropics and sub-tropics. Critical questions and gaps in public health and policy need to be addressed if major progress is to be made towards reducing the negative impact of snakebite, particularly in the World Health Organisation (WHO) Africa region. We engaged key stakeholders to identify barriers to evidence-based snakebite decision making and to explore how development of research and policy hubs could help to overcome these barriers. We conducted an electronic survey among 73 stakeholders from ministries of health, health facilities, academia and non-governmental organizations from 15 countries in the WHO Africa region. The primary barriers to snakebite research and subsequent policy translation were limited funds, lack of relevant data, and lack of interest from policy makers. Adequate funding commitment, strong political will, building expert networks and a demand for scientific evidence were all considered potential factors that could facilitate snakebite research. Participants rated availability of antivenoms, research skills training and disease surveillance as key research priorities. All participants indicated interest in the development of research and policy hubs and 78% indicated their organization would be willing to actively participate. In conclusion, our survey affirms that relevant stakeholders in the field of snakebite perceive research and policy hubs as a promising development, which could help overcome the barriers to pursuing the WHO goals and targets for reducing the burden of snakebite

Snakebite epidemiology, outcomes and multi-cluster risk modelling in Eswatini

Halving snakebite morbidity and mortality by 2030 requires countries to develop both prevention and treatment strategies. The paucity of data on the global incidence and severity of snakebite envenoming causes challenges in prioritizing and mobilising resources for snakebite prevention and treatment. In line with the World Health Organisation's 2019 Snakebite Strategy, this study sought to investigate Eswatini's snakebite epidemiology and outcomes, and identify the socio-geographical factors associated with snakebite risk. Programmatic data from the Ministry of Health, Government of Eswatini 2019-2021, was used to assess the epidemiology and outcomes of snakebite in Eswatini. We developed a snake species richness map from the occurrence data of all venomous snakes of medical importance in Eswatini that was subjected to niche modelling. We formulated four risk indices using snake species richness, various geospatial datasets and reported snakebites. A multivariate cluster modelling approach using these indices was developed to estimate risk of snakebite and the outcomes of snakebite in Eswatini. An average of 466 snakebites was recorded annually in Eswatini. Bites were recorded across the entire country and peaked in the evening during summer months. Two cluster risk maps indicated areas of the country with a high probability of snakebite and a high probability of poor snakebite outcomes. The areas with the highest rate of snakebite risk were primarily in the rural and agricultural regions of the country. These models can be used to inform better snakebite prevention and treatment measures to enable Eswatini to meet the global goal of reducing snakebite morbidity and mortality by 50% by 2030. The supply chain challenges of antivenom affecting southern Africa and the high rates of snakebite identified in our study highlight the need for improved snakebite prevention and treatment tools that can be employed by health care workers stationed at rural, community clinics. [Abstract copyright: Copyright: © 2023 Padidar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Gut microbiota and sirtuins in obesity-related inflammation and bowel dysfunction

Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS), which controls virtually all gut functions. Recent studies have revealed that the gut microbiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gut microbiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered

Modeling approaches for addressing unrelaxable bound constraints with unconstrained optimization methods

We explore novel approaches for solving nonlinear optimization problems with unrelaxable bound constraints, which must be satisfied before the objective function can be evaluated. Our method reformulates the unrelaxable bound-constrained problem as an unconstrained optimization problem that is amenable to existing unconstrained optimization methods. The reformulation relies on a domain warping to form a merit function; the choice of the warping determines the level of exactness with which the unconstrained problem can be used to find solutions to the bound-constrained problem, as well as key properties of the unconstrained formulation such as smoothness. We develop theory when the domain warping is a multioutput sigmoidal warping, and we explore the practical elements of applying unconstrained optimization methods to the formulation. We develop an algorithm that exploits the structure of the sigmoidal warping to guarantee that unconstrained optimization algorithms applied to the merit function will find a stationary point to the desired tolerance

Derivative-free optimization of a rapid-cycling synchrotron

We develop and solve a constrained optimization model to identify an integrable optics rapid-cycling synchrotron lattice design that performs well in several capacities. Our model encodes the design criteria into 78 linear and nonlinear constraints, as well as a single nonsmooth objective, where the objective and some constraints are defined from the output of Synergia, an accelerator simulator. We detail the difficulties of optimizing within the 32-dimensional, simulation-constrained decision space and establish that the space is nonempty. We use a derivative-free manifold sampling algorithm to account for structured nondifferentiability in the objective function. Our numerical results quantify the dependence of approximate solutions on constraint parameters and the effect of the form of objective function