OBJECTIVE: Our objective was to define phenotypes of non-lesional late-onset epilepsy (NLLOE) depending on its presumed aetiology and to determine their seizure and cognitive outcomes at 12 months.
METHODS: In all, 146 newly diagnosed NLLOE patients, >50 years old, were prospectively included and categorized by four presumed aetiological subtypes: neurodegenerative subtype (patients with a diagnosis of neurodegenerative disease) (n = 31), microvascular subtype (patients with three or more cardiovascular risk factors and two or more vascular lesions on MRI) (n = 39), inflammatory subtype (patient meeting international criteria for encephalitis) (n = 9) and unlabelled subtype (all individuals who did not meet the criteria for other subtypes) (n = 67). Cognitive outcome was determined by comparing for each patient the proportion of preserved/altered scores between initial and second neuropsychological assessment.
RESULTS: The neurodegenerative subtype had the most severe cognitive profile at diagnosis with cognitive complaint dating back several years. The microvascular subtype was mainly evaluated through the neurovascular emergency pathway. Their seizures were characterized by transient phasic disorders. Inflammatory subtype patients were the youngest. They presented an acute epilepsy onset with high rate of focal status epilepticus. The unlabelled subtype presented fewer comorbidities with fewer lesions on brain imaging. The neurodegenerative subtype had the worst seizure and cognitive outcomes. In other groups, seizure control was good under antiseizure medication (94.7% seizure-free) and cognitive performance was stabilized or even improved.
CONCLUSIONS: This new characterization of NLLOE phenotypes raises questions regarding the current International League Against Epilepsy aetiological classification which does not individualize neurodegenerative and microvascular aetiology per se.

BACKGROUND: Despite significant changes in healthcare, work practices, and leisure activity, the proposed precipitating factors for abdominal wall hernias have remained largely unchanged for almost two centuries. We aimed to investigate if there have been shifts in these factors over time by examining patients\' perception of precipitating factors for abdominal wall hernia development. This study was conducted in the Royal College of Surgeons In Ireland Department of Surgery, Connolly Hospital, Blanchardstown, Dublin, where patients with abdominal wall hernias completed a questionnaire  .
RESULTS: A total of 277 patients (mean age 55.7; 85.6% male) with abdominal wall hernia completed the questionnaire (66.1% inguinal; 10.8% umbilical; 6.9% paraumbilical; 10.5% epigastric; 3.2% incisional; 1.4% femoral, and 1.1% port-site). One hundred and twenty patients (43.3%) believed their hernia was due to lifting, 71 (25.6%) cited gym activity and 17 (6.1%) cited other sporting activities as the precipitating factor. Traditional factors - chronic cough and constipation - were cumulatively cited only by 11 patients (4.0%), while prostatic obstruction was not cited by any.
CONCLUSIONS: This study suggests that fitness pursuits may be an increasing contributor to the development of abdominal wall hernia. Greater attention should be paid to the proper use of gym equipment to minimise the risk of hernia development.

Acute hyperammonaemia is a medical emergency as it can progress to cerebral oedema, seizures, coma and death. Hepatic encephalopathy secondary to cirrhotic disease or portosystemic shunting are relatively well-known causes, but non-cirrhotic aetiologies of acute hyperammonaemia are less well-known, especially in the emergency department. However, an elevated ammonia is not required to make the diagnosis of hepatic encephalopathy. Although measurement of plasma ammonia is recommended for patients with acute, unexplained, altered mental status, as early identification allows early effective management which may prevent irreversible brain damage, there is currently reduced awareness among physicians of the non-cirrhotic aetiologies of acute hyperammonaemia. Furthermore, measurement of ammonia in patients with cirrhosis has been shown to have low sensitivity and specificity, and not to have altered management in the majority of cases; thus, measurement of ammonia is currently not recommended in guidelines for management of hepatic encephalopathy. We sought to describe the pathophysiology of hyperammonaemia and review the non-cirrhotic causes. This was achieved by review of MEDLINE, PubMed and Web of Science databases to include published English literature within the last 20 years. We also present a framework for investigating the acute non-cirrhotic causes of hyperammonaemia to assist both chemical pathologists and clinicians managing these often challenging cases.

Alzheimer\'s disease is a neurodegenerative problem with progressive loss of memory and other cognitive function disorders resulting in the imbalance of neurotransmitter activity and signaling progression, which poses the need of the potential therapeutic target to improve the intracellular signaling cascade brought by kinases. Protein kinase plays a significant and multifaceted role in the treatment of Alzheimer\'s disease, by targeting pathological mechanisms like tau hyperphosphorylation, neuroinflammation, amyloid-beta production and synaptic dysfunction. In this review, we thoroughly explore the essential protein kinases involved in Alzheimer\'s disease, detailing their physiological roles, regulatory impacts, and the newest inhibitors and compounds that are progressing into clinical trials. All the findings of studies exhibited the promising role of kinase inhibitors in the management of Alzheimer\'s disease. However, it still poses the need of addressing current challenges and opportunities involved with this disorder for the future perspective of kinase inhibitors in the management of Alzheimer\'s disease. Further study includes the development of biomarkers, combination therapy, and next-generation kinase inhibitors with increased potency and selectivity for its future prospects.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, and can lead to hepatocellular carcinoma (HCC), a leading cause of cancer-related death. We aimed to determine the extent to which MASLD is an increasing cause of HCC in Sweden and to determine clinical characteristics associated with underlying MASLD. Using the Swedish quality registry for liver cancer (SweLiv), we identified all adults with a diagnosis of HCC in Sweden between 2012 and 2018. Baseline data were retrieved from SweLiv and other nationwide registers. Totally, 3494 patients with HCC were identified. Of them, 757 patients (22%) had MASLD-HCC. The proportion with MASLD-HCC increased from 19% in 2012 to 25% in 2018 (ptrend = 0.012), and MASLD was since 2017 the leading cause of HCC, surpassing hepatitis C. MASLD was the fastest growing cause of HCC with a 33% increment during the study period. Compared to other patients with HCC, those with MASLD-HCC were older (75 vs. 67 years, p < .001), less commonly had cirrhosis (61% vs. 82%, p < .001), had larger tumours (median 5.5 vs. 4.3 cm, p < .001), and more often extrahepatic metastasis (22% vs. 16%, p < .001). Patients with HCC caused by MASLD or by other causes were equally likely to be diagnosed in an early stage (Barcelona Clinic Liver Cancer 0-A, 27% vs. 30%, p = .129). MASLD is now the leading cause of HCC in Sweden.

Rheumatoid arthritis (RA) is a complex chronic inflammatory illness that affects the entire physiology of human body. It has become one of the top causes of disability worldwide. The development and progression of RA involves a complex interplay between an individual\'s genetic background and various environmental factors. In order to effectively manage RA, a multidisciplinary approach is required, as this disease is complicated and its pathophysiological mechanism is not fully understood yet. In majority of arthritis patients, the presence of abnormal B cells and autoantibodies, primarily anti-citrullinated peptide antibodies and rheumatoid factor affects the progression of RA. Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton\'s tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B-lineage cells by preventing BCR activation, FC-receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in vitro and in vivo studies conducted using diverse animal models. This review focuses on BTK inhibition mechanism and its possible impact on immune-mediated disease, along with the types of RA currently being investigated, preclinical and clinical studies and future prospective.

BACKGROUND: Penile trauma is associated with debilitating complications. Apart from its sparse literature, contextually relevant evidence on aetiology and standardized severity grading, and its stratification by legal age are needed. This study aimed to describe the frequency, aetiology and injury severity grade of patients, and explore the association of specific factors by legal age.
METHODS: A single-centre retrospective cross-sectional study was conducted in our centre. Male patients with penile trauma managed by urologists were included. Data on age, year of presentation, aetiology, penile injury extent and co-existing genitourethral injuries were obtained. Descriptive and inferential statistics were undertaken using SPSS and MedCalc. Pvalue < 0.05 was considered significant.
RESULTS: Forty-two patient records were analyzed. The median age and interquartile range for legal minors and legal adults were 9.5 (5.0-14.8) years and 31.0 (22.5-41.0) years, and they constituted 28.6% (n=12) and 71.4% (n=30) of the study population respectively. Penile trauma was isolated in 26.2% (n=11) of the total population.Its annual frequency was below the median volume between 2001 and 2008 but shifted to a rate above the average level between 2017 and 2021. The rate of conveyor belt-related aetiology and high-grade trauma was 41.7% and 75.0% in legal minors while it was 26.1% and 53.3% respectively in legal adults.
CONCLUSIONS: Grade IV trauma was the most predominant while conveyor belt injury was the most common cause of the injury. Albeit limitations of statistical comparison, the rate of conveyor belt injury and high-grade trauma was numerically high in legal minors.
BACKGROUND: Les traumatismes du pénis sont associés à des complications débilitantes. Outre la rareté de la littérature, des preuves contextuel l ement per tinentes sur l \' étiol ogie et l a classification standardisée de la gravité, ainsi que leur stratification par âge légal, sont nécessaires. Cette étude visait à décrire la fréquence, l\'étiologie et le degré de gravité des blessures des patients, et à explorer l\'association de facteurs spécifiques par âge légal.
UNASSIGNED: Une étude rétrospective transversale monocentrique a été réalisée dans notre centre. Les patients masculins ayant subi un traumatisme pénien pris en charge par des urologues ont été inclus. Les données sur l\'âge, l\'année de présentation, l\'étiologie, l\'étendue de la blessure pénienne et les blessures génito-urétrales coexistantes ont été obtenues. Des statistiques descriptives et inférentielles ont été réalisées à l\'aide de SPSS et MedCalc. Une valeur de p < 0,05 a été considérée comme significative.
UNASSIGNED: Quarante-deux dossiers de patients ont été analysés. L\'âge médian et l\'intervalle interquartile pour les mineurs légaux et les adultes légaux étaient de 9,5 (5,0-14,8) ans et 31,0 (22,5-41,0) ans, représentant respectivement 28,6 % (n=12) et 71,4 % (n=30) de la population étudiée. Le traumatisme pénien était isolé chez 26,2 % (n=11) de la population totale. Sa fréquence annuelle était inférieure au volume médian entre 2001 et 2008, mais a dépassé le niveau moyen entre 2017 et 2021. Le taux d\'étiologie liée aux tapis roulants et de traumatismes graves était de 41,7 % et 75,0 % chez les mineurs légaux, contre 26,1 % et 53,3 % respectivement chez les adultes légaux.
CONCLUSIONS: Le traumatisme de grade IV était le plus prédominant, tandis que les blessures causées par les tapis roulants étaient la cause la plus courante de lésion. Bien que limitées par des comparaisons statistiques, les taux de blessures par tapis roulant et de traumatismes graves étaient numériquement élevés chez les mineurs légaux.
UNASSIGNED: Facteurs d\'âge, Étiologie, Score de gravité des blessures, Pénis.

BACKGROUND: Diarrheal diseases substantially affect public health impact in low- and middle-income countries (LMIC), particularly in Africa, where previous studies have indicated a lack of comprehensive data. With a growing number of primary studies on enteric infections in Africa, this study aimed to estimate the incidence and mortality of diarrheal pathogens across all ages in Africa in the year 2020. We also explored different methodological assumptions to allow comparison with other approaches.
METHODS: Through a systematic review and meta-analysis of data from African LMICs, we estimated the etiology proportions for diarrheal diseases and deaths. We combined the etiology proportions with incidence data collected from a population survey in Africa from 2020 and mortality data from the Global Health Observatory of WHO.
RESULTS: We estimated 1,008 billion diarrhea cases (95% UI 447 million-1,4 billion) and 515,031 diarrhea deaths (95% UI 248,983-1,007,641) in the African region in 2020. In children under five, enteroaggregative E. coli (EAEC) (44,073 cases per 100,000 people, 95% UI 18,818 - 60,922) and G. lamblia (36,116 cases per 100,000 people, 95% UI 15,245 - 49,961) were the leading causes of illness. Enteroinvasive E. coli (EIEC) (155 deaths per 100,000 people, 95% UI 106.5-252.9) and rotavirus (61.5 deaths per 100,000 people, 95% UI 42.3-100.3) were the primary causes of deaths. For children over five and adults, Salmonella spp. caused the largest number of diarrheal cases in the population of children ≥ 5 and adults (122,090 cases per 100,000 people, 95% UI 51,833 - 168,822), while rotavirus (16.4 deaths per 100,000 people, 95% UI 4.2-36.7) and enteroaggregative E. coli (EAEC) (14.6 deaths per 100,000 people, 95% UI 3.9-32.9) causing the most deaths. Geographically, the highest incidence of diarrhea was in Eastern Africa for children under five (114,389 cases per 100,000 people, 95% UI 34,771 - 172,884) and Central Africa for children over five and adults (117,820 cases per 100,000 people, 95% UI 75,111-157,584). Diarrheal mortality was highest in Western Africa for both children below five and above (children < 5: 194.5 deaths per 100,000 people, 95% UI 120-325.4; children ≥ 5 and above: 33.5 deaths per 100,000 people, 95% UI 12.9-75.1).
CONCLUSIONS: These findings provide new information on the incidence and mortality of sixteen pathogens and highlight the need for surveillance and control of diarrheal infectious diseases in Africa. The cause-specific estimates are crucial for prioritizing diarrheal disease prevention in the region.

BACKGROUND: Non-shockable in-hospital cardiac arrest (IHCA) is a condition with diverse aetiology, predictive factors, and outcome. This study aimed to compare IHCA with initial asystole or pulseless electrical activity (PEA), focusing specifically on their aetiologies and the significance of predictive factors.
METHODS: Using the Swedish Registry of Cardiopulmonary Resuscitation, adult non-shockable IHCA cases from 2018 to 2022 (n = 5788) were analysed. Exposure was initial rhythm, while survival to hospital discharge was the primary outcome. A random forest model with 28 variables was used to generate permutation-based variable importance for outcome prediction.
RESULTS: Overall, 60% of patients (n = 3486) were male and the median age was 75 years (IQR 67-81). The most frequent arrest location (46%) was on general wards. Comorbidities were present in 79% of cases and the most prevalent comorbidity was heart failure (33%). Initial rhythm was PEA in 47% (n = 2702) of patients, and asystole in 53% (n = 3086). The most frequent aetiologies in both PEA and asystole were cardiac ischemia (24% vs. 19%, absolute difference [AD]: 5.4%; 95% confidence interval [CI] 3.0% to 7.7%), and respiratory failure (14% vs. 13%, no significant difference). Survival was higher in asystole (24%) than in PEA (17%) (AD: 7.3%; 95% CI 5.2% to 9.4%). Cardiopulmonary resuscitation (CPR) durations were longer in PEA, 18 vs 15 min (AD 4.9 min, 95% CI 4.0-5.9 min). The duration of CPR was the single most important predictor of survival across all subgroup and sensitivity analyses. Aetiology ranked as the second most important predictor in most analyses, except in the asystole subgroup where responsiveness at cardiac arrest team arrival took precedence.
CONCLUSIONS: In this nationwide registry study of non-shockable IHCA comparing asystole to PEA, cardiac ischemia and respiratory failure were the predominant aetiologies. Duration of CPR was the most important predictor of survival, followed by aetiology. Asystole was associated with higher survival compared to PEA, possibly due to shorter CPR durations and a larger proportion of reversible aetiologies.

Pain can be defined as an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage. Though consistent with this definition, different types of pain result in different behavioural and psychophysiological responses. For example, the transient, non-threatening, acute muscle pain element of exercise-induced pain (EIP) is entirely different from other pain types like delayed onset muscle soreness, muscular injury or chronic pain. However, studies often conflate the definitions or assume parity between distinct pain types. Consequently, the mechanisms through which pain might impact exercise behaviour across different pain subcategories may be incorrectly assumed, which could lead to interventions or recommendations that are inappropriate. Therefore, this review aims to distinguish EIP from other subcategories of pain according to their aetiologies and characteristics, thereby providing an updated conceptual and operational definition of EIP. Secondly, the review will discuss the experimental pain models currently used across several research domains and their relevance to EIP with a focus on the neuro-psychophysiological mechanisms of EIP and its effect on exercise behaviour and performance. Finally, the review will examine potential interventions to cope with the impact of EIP and support wider exercise benefits. HIGHLIGHTS: What is the topic of this review? Considerations for future research focusing on exercise-induced pain within endurance exercise settings. What advances does it highlight? An updated appraisal and guide of research concerning exercise-induced pain and its impact on endurance task behaviour, particularly with reference to the aetiology, measurement, and manipulation of exercise-induced pain.