Severe Long-term Complications Research Articles

Surgical Complications Following Renal Transplantation in a Large Institutional Cohort.

Successful renal transplantation (RTx) relies on immunosuppression and an optimal surgical course with few surgical complications. Studies reporting the postoperative complications after RTx are heterogeneous and often lack systematic reporting of complications. This study aims to describe and identify postoperative short-term and long-term complications after RTx in a large institutional cohort and identify risk factors for a complicated surgical course. The study is a retrospective single-center cohort of 571 recipients who underwent living or deceased donor open RTx between 2014 and 2021. Data were collected on background information and perioperative and postoperative data. Complications were defined as short-term (<30 d) or long-term (>30 d) after transplantation and graded according to the Clavien-Dindo classification. Multivariable logistic regression was performed to evaluate risk factors for serious short-term complications and multivariable time-dependent Cox regression to evaluate risk factors for long-term complications. A total of 351 patients received a graft from a deceased donor, and 144 of these grafts were on perfusion machine before transplantation. One or more short-term complications occurred in 345 (60%) patients. Previous RTx was associated with short-term Clavien-Dindo >2 complications in recipients (odds ratio = 2.08; 95% confidence interval [CI], 1.18-3.69; P = 0.01). Being underweight (body mass index <18.5) in combination with increasing age increased the odds of short-term Clavien-Dindo >2 and vascular complications. Increasing blood loss per 100 mL was associated with increased odds of short-term Clavien-Dindo >2 (odds ratio = 1.11; 95% CI, 1.01-1.21; P = 0.032). No associations were found for long-term complications after RTx. The 5-y cumulative incidence of graft loss was 12.6% (95% CI, 8.9-16.3). Short-term complications are common after RTx, and risk factors for severe short-term complications include previous RTx, increasing age, and low body mass index. No risk factors were identified for severe long-term complications. Further studies should explore whether new surgical techniques can reduce surgical complications in RTx.

A Case of Posterior Pharyngeal Wall Perforation After Blunt Neck Trauma

Perforation of the pharynx due to external blunt trauma is an uncommon type of pharyngeal injury. It can lead to serious complications such as deep neck infection, sepsis, mediastinitis, and even mortality if not promptly recognized and treated. Therefore, early diagnosis and treatment are crucial to prevent severe consequences and long-term complications. If the size of the injury is less than 2 cm and there is no invasion of the esophagus or mediastinum, conservative, nonsurgical treatment may be appropriate. In this case report, we present a case of retropharyngeal wall perforation following external blunt neck trauma with literature review.

Case Series Report: Subarachnoid Hemorrhage and ICU Management

Background: Subarachnoid hemorrhage is a neurological syndrome with complex systemic complications. Rupture of an intracranial aneurysm causes acute extravasation of arterial blood under high pressure into the subarachnoid space and often into the brain parenchyma and ventricles. Bleeding triggers a complex series of events, which can ultimately lead to early brain injury, delayed cerebral ischemia, and systemic complications. Cases: There were six cases of subarachnoid hemorrhage. Some patients come clinically with severe headache and loss of consciousness. The patient has been treated quickly and aggressively and even put on a ventilator for complications of respiratory failure, support for shock and management of aneurysm clipping and EVD. Rapid and precise diagnosis in the management of patients with SAH is of paramount importance, within the first few hours after the onset of SAH. The risk for early neurologic damage and high rates of severe long-term complications necessitated aggressive early management. Conclusion: Rapid diagnosis and attentive management of patients with SAH are essential, as early deterioration is possible within the first few hours after the onset of SAH. The risk for early neurologic damage and high rates of severe long-term complications necessitated aggressive early management. Prevention and Management of Complications. The most common complications were pneumonia, aspiration, respiratory failure/distress, sepsis and imbalance electrolyte (hyponatremia). Approximately 50% of deaths after SAH are due to medical complications.

The CNS Microenvironment Promotes Leukemia Cell Survival By Disrupting Tumour Suppression and Cell Cycle Regulation in Pediatric T-Cell Acute Lymphoblastic Leukemia

Although modern treatment has improved the overall survival of pediatric T-cell acute lymphoblastic leukemia (T-ALL) greatly, more than 20% of all children diagnosed with T-ALL relapse (Fattizzo et al., 2020). Approximately 30% of all relapse cases occur in the central nervous system (CNS) and CNS involvement is considered a major risk factor for treatment failure and increased mortality (Frishman-Levy &amp; Izraeli, 2017). To date, CNS directed therapy is considered essential for complete cure to prevent relapse in the CNS, leading to severe neurotoxic effects and long-term adverse complications (Thastrup et al., 2022). Due to lack of knowledge regarding the mechanisms promoting leukemia survival in the CNS and absence of reliable biomarkers to predict CNS involvement, the development of new therapeutic drugs able to eradicate leukemia cells in the CNS is not progressing, therefor limiting the overall survival of pediatric T-ALL patients (Thastrup et al., 2022). To identify genetic alterations in CNS involved T-ALL we performed an RNA-sequencing analysis coupled with a gene set enrichment analysis (GSEA) studying pediatric T-ALL patient samples obtained from the TARGET initiative. We included 30 samples from patients at initial diagnosis subdivided by degree of CNS involvement, ranging from CNS1 (no CNS disease) to CNS3 (advanced CNS disease), as well as 13 samples from patients who had relapsed in the CNS. Our analysis identified distinct genetic alterations in CNS involved T-ALL and CNS relapse compared to diagnosis samples without CNS implications, with dysregulation of genes involved in tumour suppression, apoptosis and self-renewal. CNS relapsed patients were distinguished from diagnosis patients by a distinct gene expression pattern, with an upregulation of many genes, including cell cycle inhibitor CDKN2A and transcription factor HOXA3 (Figure 1A). We also found disruption of many signaling pathways, including enrichment of the p53 pathway in patients who relapsed in the CNS compared to non-CNS involved diagnosis patients. To further study the effects of CNS implications in pediatric T-ALL, we established a co-culture of pediatric T-ALL cell lines (n=4) and a glioblastoma cell line (U87-MG). Following co-culture, changes to mRNA expression was evaluated by RT-qPCR, revealing dysregulation of many genes, including an upregulation of cancer stem cell marker and cell adhesion molecule CD44 (Chen et al., 2018). Moreover, T-ALL cells grown in CNS co-culture displayed a downregulation of tumour suppressor TP53 and an upregulation of its negative regulator, proto-oncogene MDM2 when compared to cells grown in suspension (Figure 1B) (Hernandez Borrero &amp; El-Deiry, 2021). Co-culture also induced pro-survival isoform switching of BCL2L1 (BCLX), part of the BCL family of apoptotic regulators (Daniel et al., 2013). Together, these results suggest an increased survival and loss of tumour suppression of T-ALL cells when grown in direct contact with CNS derived cells. To determine effects of the CNS microenvironment on therapy resistance, T-ALL cell lines grown in co-culture were exposed to 2µM methotrexate, a chemotherapeutic agent used during CNS directed therapy (Thastrup et al., 2022). Leukemia cells in co-culture displayed an increased survival compared to cells grown in suspension following 48 hours of methotrexate exposure, as well as dysregulation of several genes involved in cell survival, self-renewal and cell cycle regulation. Cyclins and CDKs involved in controlling cell cycle progression were differentially expressed in co-culture versus suspension, with a downregulation of CDK2 and cyclin A, crucial for S/G2 transition, as well as CDK1 and cyclin B, responsible for G2/M transition (Leal-Esteban &amp; Fajas, 2020). These results indicate a shift towards cell cycle arrest and senescence of T-ALL cells during methotrexate exposure in CNS co-culture, potentially promoting leukemia survival and chemoresistance. Taken together, our findings indicate a differential gene expression pattern in CNS involved T-ALL, which could potentially be utilized as predicative biomarkers to properly identify patients at risk of CNS relapse. CNS co-culture revealed cell cycle alterations and loss of proliferation markers, promoting senescence and therapy resistance, which could serve as potential therapeutic targets.

Development of a gastrocutaneous fistula from a marginal ulcer after repair of duodenal injury with pyloric exclusion

Duodenal trauma is rare but can be associated with significant morbidity and mortality (Pandey et al., 2011) [1]. Adjunct procedures, such as pyloric exclusion, can be performed to assist in surgical repair of these injuries. However, pyloric exclusion can lead to severe long-term complications associated with significant morbidity that can be difficult to repair. A 35-year-old man with a history of duodenal trauma from a gunshot wound (GSW) status post pyloric exclusion and Roux-en-Y gastrojejunostomy presented to the Emergency Department (ED) with complaints of abdominal pain and leakage of food particles and fluid from an open wound around his surgical scar. Computed tomography (CT) scan on admission showed a tract extending from the gastrojejunostomy anastomosis to the skin representing a fistula. Esophago-gastro-duodenoscopy (EGD) reconfirmed a large marginal ulcer that had fistulized to the skin. After nutritional repletion, the patient was taken to the operating room (OR) for takedown of the enterocutaneous fistula and Roux-en-Y gastrojejunostomy, closure of gastrostomy and enterotomy, pyloroplasty and feeding jejunostomy tube placement. The patient was re-admitted after discharge with abdominal pain, vomiting and early satiety. EGD showed gastric outlet obstruction and severe pyloric stenosis which was managed with endoscopic balloon dilation. This case represents the severe and potentially life-threatening complications that may occur after pyloric exclusion with Roux-en-Y gastrojejunostomy. Gastrojejunostomies are prone to marginal ulceration which can perforate if not adequately treated. Free perforations cause peritonitis, but if the perforation is contained it can erode through the abdominal wall creating the rare complication of a gastrocutaneous fistula. Even after restoration of normal anatomy with a pyloroplasty, patients may suffer additional complications such as pyloric stenosis requiring continued intervention.

Exploring causal mechanisms and essential factors in the prevention and control of chlamydia in Guangdong, Southern China: a study protocol

BackgroundChlamydia Trachomatis (CT) is among the most prevalent sexually transmitted diseases (STDs) globally. According to the World Health Organization, more than 131 million people get infected with CT annually. CT is usually transmitted via sexual contact or perinatal exposure and can result in severe long-term complications. In developing nations, particularly, the prevention and control of CT is challenging. Hence, this study will explore the feedback mechanisms of chlamydia prevention and control, as well as identify the essential factors affecting the control and prevention of this infection in China.MethodsOur study will employ a mixed-methods research design that encompasses both qualitative and quantitative methods. Firstly, we will develop a causal loop diagram (CLD) based on the literature review and optimize it via in-depth interviews with stakeholders. Additionally, we will utilize a quantitative method called MICMAC(Impact Matrix Cross-Reference Multiplication Applied to a Classification tool) to obtain consensus among different stakeholders and pinpoint the key information. Next, the CLD will be transformed into a system dynamics model (SDM) to evaluate the feedback mechanisms within the CLD. The causality in the CLD will be modeled using mathematical equations, which facilitate the transformation into an SDM. As such, we will be able to analyze the dynamic behavior of the system and its response to different decisions.DiscussionOur study offers a systematic perspective on the control and prevention of chlamydia infection through system dynamics modeling, examining the dynamic properties and background factors of the system. The creation of the CLD affords stakeholders the chance to comprehend the functionality of their relationships and improve cooperation. Consequently, by evaluating the outcomes of these simulations, it will be possible to analyze and determine potential interventions and their effects on chlamydia infections. This modeling approach can help us gain insight into the dynamic characteristics of the system, evaluate the potential outcomes of different decisions, and design control strategies to either stabilize the system or adjust its behavior.

Unmet Needs in the Treatment of Childhood Type 2 Diabetes: A Narrative Review.

Type 2 diabetes (T2D) in youth is a global health concern characterized by an increasing incidence and prevalence, especially among disadvantaged socioeconomic subgroups. Moreover, youth-onset T2D is more aggressive and causes earlier, more severe long-term cardio-renal complications compared with T2D in adults. The therapeutic options available are limited and often inadequate, partially due to the numerous challenges in implementing clinical trials for this vulnerable patient population. Over the last few years, a significant effort has been made to develop new effective drugs for children and adolescents with T2D. Specifically, a number of studies are currently generating new data to address the urgent unmet medical need for optimal management of this disease. This review describes the central features of youth-onset T2D and summarizes the available treatments and ongoing studies in pediatric patients.

Hypoparathyroidism-related health care utilization and expenditure during the first postoperative year after total thyroidectomy for cancer: a comprehensive national cohort study.

Hypoparathyroidism is the most common complication of total thyroidectomy for cancer, and requires calcium and/or vitamin D supplementation for an unpredictable period of time. The additional cost associated with this complication has not hitherto been assessed. The aim of this study was to assess the economic burden of postoperative hypoparathyroidism after total thyroidectomy for cancer in France. Based on the French national cancer cohort, which extracts data from the French National Health Data System (SNDS), all adult patients who underwent a total thyroidectomy for cancer in France between 2011 and 2015 were identified, and their healthcare resource use during the first postoperative year was compared according to whether they were treated postoperatively with calcium and/or vitamin D or not. Univariate and multivariate cost analyses were performed with the non-parametric Wilcoxon test and generalized linear model (gamma distribution and log link), respectively. Among the 31,175 patients analyzed (75% female, median age: 52y), 13,247 (42%) started calcium and/or vitamin D supplementation within the first postoperative month, and 2,855 patients (9.1%) were still treated at 1 year. Over the first postoperative year, mean overall and specific health expenditures were significantly higher for treated patients than for untreated patients: €7,233 vs €6,934 per patient (p<0.0001) and €478.6 vs €332.7 per patient (p<0.0001), respectively. After adjusting for age, gender, Charlson Comorbidity index, ecological deprivation index, types of thyroid resection, lymph node dissection and complications, year and region, the incremental cost of overall health care utilization was €142 (p<0.004). Our study found a significant additional cost in respect of health expenditures for patients who had hypoparathyroidism after thyroidectomy for cancer, over the first postoperative year. Five-year follow-up is planned to assess the impact of more severe long-term complications on costs.

An Update on Familial Mediterranean Fever.

(1) Background: Familial Mediterranean Fever (FMF) is the prototypal autoinflammatory disease, characterized by recurrent bursts of neutrophilic inflammation. (2) Methods: In this study we look at the most recent literature on this condition and integrate it with novel information on treatment resistance and compliance. (3) Results: The canonical clinical presentation of FMF is in children with self-limited episodes of fever and polyserositis, associated with severe long-term complications, such as renal amyloidosis. It has been described anecdotally since ancient times, however only recently it has been characterized more accurately. We propose an updated overview on the main aspects of pathophysiology, genetics, diagnosis and treatment of this intriguing disease. (4) Conclusions: Overall, this review presents the all the main aspects, including real life outcome of the latest recommendation on treatment resistance of FMF, a disease, that not only helped understanding the pathophysiology of the auto inflammatory process but also the functioning of the innate immune system itself.

High levels of pro-inflammatory SARS-CoV-2-specific biomarkers revealed by in vitro whole blood cytokine release assay (CRA) in recovered and long-COVID-19 patients.

Cytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19. In this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis. A total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)-categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation. Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1β, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1β and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1β, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals. We revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination.

Rising incidence of iatrogenic bile duct injuries following cholecystectomy: a cause of worry

Inaccurate learning and understanding of biliary anatomy mainly lead to iatrogenic bile duct injuries (IBDI) and such complications are mostly the postoperative result of laparoscopic cholecystectomy. Minor bile leakage of aberrant ducts and complete occlusion of the main duct or a branch (often an aberrant right duct) are possibilities for many IBDIs. In addition, bile duct strictures and biliary leakages are severe long-term complications after laparoscopic cholecystectomy1. A well-established thought is that any postoperative change observed after laparoscopic cholecystectomy suggests possible damage to the biliary tract. Injuries related to the biliary tract are associated with high morbidity, death rate, and prolonged hospitalization. Bile duct injury with an estimated incidence of 0.4%–1.5% is a dangerous complication of cholecystectomy2. and with the introduction of laparoscopic cholecystectomy as the surgical treatment of choice for symptomatic cholelithiasis, the incidence of IBDI—which represents the most dramatic complications after open or laparoscopic cholecystectomy increased3. Comparing the incidence of IBDI in open cholecystectomy and laparoscopic cholecystectomy, despite increasing experience, IBDI incidence is still elevated in LC which is up to 3% compared with the rate of clinically relevant bile leaks after conventional open cholecystectomy ranging between 0.1 and 0.54–6. According to studies, the incidence of bile duct injuries after laparoscopic cholecystectomy hiked as high as 1% with a conservative estimate being 1 in 1000 cases (0.1%)7. Successful treatment is characterized by early diagnosis, control of the intra-abdominal fluid collection and infection, nutritional balance, multidisciplinary approach, and surgical repair by an experienced surgeon in biliary reconstruction. The top most recommended strategies to classify and initially diagnose and treat IBDI are endoscopic techniques, for example biliary stent placement, biliary sphincterotomy, and nasobiliary drainage. Surgical intervention, precisely Roux-en-Y hepaticojejunostomy, is the most feasible treatment for patients with complete dissection or obstruction of the bile duct. Even though eventually most bile duct injuries require surgical reconstruction but the role of the interventional radiologist in the initial diagnosis, classification, and management of IBDIs is often crucial for achieving a successful outcome. Long-term results are most important in the assessment of the effectiveness of IBDI treatment. Apart from that, adequate diagnosis and treatment of IBDI may avoid many serious complications and improve the quality of life of our patients, therefore, management of these injuries often requires an experienced multidisciplinary team (including interventional radiology, gastroenterology, and surgery), they are best handled in a tertiary referral center. Ethical approval None. Sources of funding None. Author contribution O.H.S., S.I.A., R.M.A., and M.K.: wrote the manuscript. ,O.H.S. and S.I.A.: review editing, formatting, and referencing, Conflict of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) None. Guarantor Maham Khan.

Female Genital Cutting or Circumcision

Woman genital slicing additionally referred to as woman genital mutilation or circumcision, is a deeply rooted cultural exercise that entails the partial or overall elimination of outside lady genitalia for non-scientific reasons. Despite being extensively criticized for its bodily and psychological fitness dangers, as well as its violation of human rights, the practice persists in various parts of the sector, specifically in Africa, the Middle East, and Asia. Female genital reduction is regularly justified inside communities as a ceremony of passage, a method of maintaining purity, or a way to control ladies’ sexuality. However, its effects are long-lasting and negative. The system can result in severe pain, bleeding, infections, and long-term period complications, which include urinary issues, headaches throughout childbirth, and mental trauma. The ethical issues surrounding this practice are obtrusive, as it infringes upon physical autonomy, sexual well-being, and gender equality. Efforts to eliminate female genital slicing span scientific, legal, and social dimensions. Several worldwide groups and governments have denounced the practice and enacted legal guidelines against it, specializing in cognizance campaigns, education, and community engagement. Grassroots projects inside affected groups have proven effective in transferring perceptions and hardening the deeply ingrained beliefs that perpetuate the exercise. To put off lady genital slicing, a holistic method is vital-one that includes not only the best criminal measures but also complete sex schooling, female empowerment, and collaboration with cultural and religious leaders. By addressing the underlying social norms and offering alternative cultural practices, societies can safeguard the rights and fitness of girls and women, letting them lead lives free from the bodily and emotional burdens of female genital reduction.

Современные возможности хирургического лечения при глазных осложнениях синдромов Стивенса — Джонсона и Лайелла

Epidermolytic drug reactions (EDR) are severe acute drug-induced allergic disorders characterized by extensive lesions of the skin and mucous membranes. Drug-induced Stevens-Johnson and Lyell's syndromes manifested with acute skin and mucous membrane disorders and often leading to lethal outcome may affect eyelids and ocular surface with different levels of severity and thus can cause serious functional ocular complications. The authors present two clinical reports of patients with ocular EDR manifestations in acute and long-term time periods and review the currently available effective treatment options for patients with such ocular complications and their consequences. The article describes surgical treatments which enabled to achieve satisfactory anatomical and functional results in patients with the above disorders. Timely treatment of Stevens-Johnson and Lyell's syndromes comprising systemic and topical conservative therapy in combination with surgical procedures during the acute stage plays an important role for the prediction of severe long-term ocular complications. The elimination of ocular complications caused by these syndromes is associated with multistage reconstructive surgery. The authors emphasize that long-term follow-up by ophthalmologist will be required for patients who survived Stevens-Johnson and Lyell's syndromes. Keywords: epidermolytic drug reactions, Stevens–Johnson syndrome, Lyell's syndrome, amniotic membrane transplantation, dry eye syndrome, pseudomembranous blepharoconjunctivitis, multistage reconstructive surgery. For citation: Chernysh V.F., Haritonova N.N., Kulikov A.N. et al. Current surgical treatment options for ocular complications of Stevens- Johnson and Lyell's syndromes. Russian Journal of Clinical Ophthalmology. 2023;23(2):99–106 (in Russ.). DOI: 10.32364/2311-7729- 2023-23-2-99-106.

Lower urinary tract injuries in patients with pelvic fractures at a level 1 trauma center – an 11-year experience

Background Urological injuries can occur in patients with pelvic fractures. Treatment recommendations lack solid evidence and is often pragmatical. There is a continuous need to describe short- and long-term morbidity following lower urinary tract trauma. Objective To describe incidence, diagnosis, treatment, and morbidity following lower urinary tract injuries in pelvic fractures. Patients and methods Retrospective study including patients with pelvic, including acetabular, fractures admitted to a Level I Trauma Centre covering 2.8 million citizens between 2009 and 2020. Outcome measurements comprised primary management, treatment trajectory, short- and long-term complications and outcomes. Results A total of 39 (5%) patients with pelvic fractures had concomitant urethral and/or bladder injuries, and one patient with an acetabular fracture had a bladder injury. The management of urethral injuries varied vastly, and complete urethral ruptures were associated with severe short- and long-term complications. Only one patient with bladder injury experienced severe long-term complications. Conclusions Management of lower urinary tract injuries in patients with major pelvic fractures remains a major challenge. Special attention should be focused on urethral injuries where we uncovered an unsystematic treatment and follow-up even in a highly experienced centre, although this is also attributed to complicated multidisciplinary patient trajectories. There is a continuous need to reduce long-term complications following urethral trauma which should be addressed in multicenter studies.

Diabetes en cardiovasculaire risicobepalingen in Belgische officina-apotheken

Diabetes and cardiovascular risk assessments in Belgian community pharmacies Type 2 diabetes mellitus (T2DM) and cardiovascular disease are major health problems related to a number of modifiable risk factors such as obesity, an unhealthy lifestyle, hypertension and hypercholesterolemia. Early detection and management of these risk factors are essential to avoid severe long-term complications. Until now, screening for risk factors for T2DM and cardiovascular diseases in Belgium has been largely the task of the general practitioner. However, various international studies show that the community pharmacist can play a complementary role in this. This article provides an overview of the Belgian projects with T2DM and cardiovascular risk assessment in pharmacies. Between 2014 and 2021, there were 5 projects with T2DM and cardiovascular risk assessment in the community pharmacy in Belgium. These projects show that community pharmacists have screening tools at their disposal to perform an adequate risk assessment. Relative to the total number of patients screened, the percentage of patients referred by the pharmacist because of a high risk for T2DM varied between 25% and 58%. In 1 project with an additional cardiovascular risk assessment, 63% was referred because of an increased risk for cardiovascular disease. These results highlight the potential for the pharmacist’s role in the prevention of DM and cardiovascular diseases. Due to their proximity and accessibility, pharmacists can play an important complementary social role in the early recognition of chronic diseases in people who do not or irregularly use medical care.

“It sounds very negative”: Patient perspectives on de-escalation of treatment concept and language.

254 Background: As the combination of systemic and targeted chemotherapies is associated with severe adverse side effects and long-term health complications, there is interest in reducing treatment intensity for patients with early-stage breast cancer (EBC). Currently, this approach is being described as “de-escalation,” though there is some concern that this language and framing are not well understood or preferred by patients. Methods: We collected qualitative interview data from twenty-four patients with Stage II-III breast cancer and sixteen patient advocates. Interviews explored interest in participation in clinical trials testing reduced amounts of chemotherapy, reactions to the word “de-escalation,” and preferred ways to describe this approach and its anticipated benefits. Interviews were audio-recorded and transcribed, and researchers used qualitative content analysis to code for dominant themes. Results: Twenty-three participants (57.5%) expressed interest in participating in a trial of reduced chemotherapy. However, 60% of participants had a negative response to the word “de-escalation,” including 78% of respondents that said they were interested in the concept. To describe this approach, respondents tend to prefer words like “personalization,” “optimization,” or “reduced chemotherapy.” Participants also expressed the importance of provider-patient communication, clear and simple language, sharing the decision-making process, and continued support throughout and after treatment in their consideration of trials testing lower amounts of chemotherapy. Conclusions: Among individuals with EBC, there is significant interest in alleviating treatment-related toxicity by reducing chemotherapeutic intensity. Patients are more apt to feel comfortable participating in trials testing this approach if they are framed in terms of customizing treatment to the individual patient and added benefit—reduced toxicities, higher quality of life during treatment and lower risk of long-term complications—rather than in terms of taking treatments away or doing less than the standard of care. “De-escalation” is not an ideal word to describe these trials as many associate this word with giving up in the war against cancer. Instead, participants prefer positive, patient-centered language. This information will be useful to providers in considering how best to describe de-escalation clinical trials to eligible patients in ways that avoid therapeutic misconception and facilitate the shared decision-making process regarding treatment.

Traumatic Brain Injury and Secondary Neurodegenerative Disease.

Traumatic brain injury (TBI) is a devastating event with severe long-term complications. TBI and its sequelae are one of the leading causes of death and disability in those under 50 years old. The full extent of secondary brain injury is still being intensely investigated; however, it is now clear that neurotrauma can incite chronic neurodegenerative processes. Chronic traumatic encephalopathy, Parkinson's disease, and many other neurodegenerative syndromes have all been associated with a history of traumatic brain injury. The complex nature of these pathologies can make clinical assessment, diagnosis, and treatment challenging. The goal of this review is to provide a concise appraisal of the literature with focus on emerging strategies to improve clinical outcomes. First, we review the pathways involved in the pathogenesis of neurotrauma-related neurodegeneration and discuss the clinical implications of this rapidly evolving field. Next, because clinical evaluation and neuroimaging are essential to the diagnosis and management of neurodegenerative diseases, we analyze the clinical investigations that are transforming these areas of research. Finally, we briefly review some of the preclinical therapies that have shown the most promise in improving outcomes after neurotrauma.

Vanishing bile duct syndrome after drug-induced liver injury

BackgroundVanishing bile duct syndrome (VBDS) is a serious cholestatic liver disease that can be a complication of drug-induced liver injury (DILI). While journals have published case reports of this condition, large studies on a cohort of these patients are lacking. We aimed to compile published case reports and case series of patients with VBDS and DILI to describe the clinical and laboratory characteristics of the disease and identify factors associated with good and poor outcomes. MethodsWe included case reports and case series of VBDS secondary only to DILI. We extracted demographic, clinical, laboratory, treatment, and exposure data from each case report and categorized cases by outcome, good versus poor. We defined poor outcomes as cases with severe long-term complications or death. We analyzed risk factors for poor outcomes using logistic regression. ResultsWe identified a total of 59 eligible cases. Of those, 39 (59%) were female, the median age was 36 (IQR:12–58), and 18 (31%) were pediatric cases (≤18 years). The most common offending drug class was antibiotics, especially beta-lactams. Patients with increased total bilirubin (OR=4.69; 95% CI=1.55–15.49; p = 0.008), increased direct bilirubin (OR=6.50; 95% CI=1.34–48.91; p = 0.034), lower liver synthetic activity (OR=0.11; 95% CI=0.02–0.55; p = 0.013), and older age (OR=3.31; 95% CI=1.15–10.04; p = 0.029) were more likely to develop poor outcomes. ConclusionsIn patients with VBDS and DILI, antibiotics were the most common offending agents. Higher total and direct bilirubin levels were associated with poor outcomes.

An interpretable neural network for outcome prediction in traumatic brain injury

BackgroundTraumatic Brain Injury (TBI) is a common condition with potentially severe long-term complications, the prediction of which remains challenging. Machine learning (ML) methods have been used previously to help physicians predict long-term outcomes of TBI so that appropriate treatment plans can be adopted. However, many ML techniques are “black box”: it is difficult for humans to understand the decisions made by the model, with post-hoc explanations only identifying isolated relevant factors rather than combinations of factors. Moreover, such models often rely on many variables, some of which might not be available at the time of hospitalization.MethodsIn this study, we apply an interpretable neural network model based on tropical geometry to predict unfavorable outcomes at six months from hospitalization in TBI patients, based on information available at the time of admission.ResultsThe proposed method is compared to established machine learning methods—XGBoost, Random Forest, and SVM—achieving comparable performance in terms of area under the receiver operating characteristic curve (AUC)—0.799 for the proposed method vs. 0.810 for the best black box model. Moreover, the proposed method allows for the extraction of simple, human-understandable rules that explain the model’s predictions and can be used as general guidelines by clinicians to inform treatment decisions.ConclusionsThe classification results for the proposed model are comparable with those of traditional ML methods. However, our model is interpretable, and it allows the extraction of intelligible rules. These rules can be used to determine relevant factors in assessing TBI outcomes and can be used in situations when not all necessary factors are known to inform the full model’s decision.

The Epidemiology of Diabetic Kidney Disease

Globally, the incidence and prevalence of diabetes mellitus has risen dramatically, owing mainly to the increase in type 2 diabetes mellitus (T2DM). In 2021, 537 million people worldwide (11% of the global population) had diabetes, and this number is expected to increase to 783 million (12%) by 2045. The growing burden of T2DM is secondary to the pandemic of obesity, which in turn has been attributed to increased intake of processed food, reduced physical activity, and increased sedentary behaviour. This so-called western lifestyle is related with the global increase in urbanization and technological development. One of the most frequent and severe long-term complications of diabetes is diabetic kidney disease (DKD), defined as chronic kidney disease in a person with diabetes. Approximately 20–50% of patients with T2DM will ultimately develop DKD. Worldwide, DKD is the leading cause of chronic kidney disease and end-stage kidney disease, accounting for 50% of cases. In addition, DKD results in high cardiovascular morbidity and mortality, and decreases patients’ health-related quality of life. In this review we provide an update of the diagnosis, epidemiology, and causes of DKD.