Early Initiation Of Treatment Research Articles

A Comprehensive Review of Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome

Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disorder, characterized by acute tubulointerstitial nephritis and uveitis. It poses diagnostic challenges due to the mostly asynchronous onset of renal and ocular manifestations, as well as the variety of differential diagnoses. This review provides an overview of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management strategies. Methods: A comprehensive review of the peer-reviewed literature, including studies and case reports, was conducted. Results: The etiology of TINU syndrome involves an autoimmune reaction to renal and ocular antigens, leading to interstitial inflammation and tubular damage in the kidneys, and anterior uveitis with acute onset of flares. Diagnostic criteria based on ocular examination, laboratory parameters, and renal biopsy emphasize the need to exclude other systemic diseases. TINU syndrome accounts for approximately 2% of all uveitis cases. Primary treatment consists of corticosteroids, while immunomodulatory therapies (methotrexate, azathioprine, mycophenolate mofetil, or biologic agents) are reserved for refractory cases. Recurrence of uveitis appears to be more common than that of nephritis. Conclusions: TINU syndrome is rare and requires clinical suspicion for accurate diagnosis. Early diagnosis and initiation of treatment are crucial for achieving favorable outcomes. Advances in the understanding of its pathogenesis and treatment have improved patient outcomes. Further research is needed to investigate the underlying triggers and mechanisms in order to develop targeted therapies.

Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023

BackgroundCerebral creatine deficiency disorders (CCDD) are rare diseases caused by defects in the enzymes L-arginine: glycine amidinotransferase (AGAT) or guanidinoacetate-N-methyltransferase (GAMT), which are involved in synthesis of creatine; or by a defect in the creatine transporter (CRTR), which is essential for uptake of creatine as important energy source into the target cells. Patients with CCDD can present with a variety of unspecific symptoms: global developmental delay, speech-language disorder, behavioral abnormalities and seizures. Early treatment initiation is essential in AGAT and GAMT deficiencies to achieve a favorable outcome. This study describes the CCDD patient cohort in a single center, and an analysis of the referrals to two Swiss laboratories in Lausanne and Zurich between 2015 and 2023 for the two marker metabolites guanidinoacetate and creatine.ResultsThe patient cohort comprised 6 patients (defects: 2 GAMT, 4 CRTR), who were initially seen by different subspecialties depending on first symptoms. There was a diagnostic and therapeutic delay between 3 and 32 months (mean 13.8). Numbers of biomarker requests showed a constant increase during the study period, with a majority of tests performed in urine, the preferred sample for CCDD detection. Almost all samples (93.3%) were sent in by large hospitals (mainly from neurology, developmental pediatrics and metabolism) and only few (5.2%) by pediatricians in private practice, although those usually see the patients first.ConclusionsThe data from this study demonstrate a relevant delay in identifying patients with these rare conditions, and a predominance of biomarker analysis requested from pediatric subspecialties that are involved in patient management often long after occurrence of symptoms. To reduce the diagnostic delay and the outcome of patients, the current practice of sample referral should be reflected and first-contact healthcare providers should be encouraged to initiate selective screening.

P0993 Prevention of Postoperative Recurrence of Crohn’s Disease: Comparison of Two Therapeutic Strategies

Abstract Background Postoperative recurrence of Crohn’s disease affects half of patients within 10 years, making prevention crucial. The ECCO recommends immediate postoperative prophylactic treatment for patients with at least one risk factor for recurrence. While this strategy is proven effective for those with multiple risk factors, data on its benefits compared to endoscopy-guided prophylaxis in patients with only one risk factor is lacking. The study aimed to compare immediate postoperative prophylactic treatment with endoscopy-guided prophylaxis in patients with a single risk factor Methods This retrospective bicentric study included patients who underwent ileocolic resection for Crohn’s disease between January 2011 and December 2021, each with one risk factor for postoperative recurrence. Patients were divided into two groups G1 received immediate postoperative prophylactic treatment, while G2 received prophylactic treatment guided by colonoscopy within the first year after surgery. The primary outcome was the frequency of endoscopic recurrence within one year :Rutgeerts score ≥ i2. Secondary outcomes included severe endoscopic recurrence (i4) within 12 months and clinical recurrence at 6 and 24 months. Statistical analysis was conducted using SPSS26 Results This study included 41 patients divided into two groups. Group 1 (24 patients) had an average age of 34 years, with 58.33% being active smokers.Postoperative treatments were as follows: infliximab (4 patients), infliximab-azathioprine combination (3 patients), adalimumab (4 patients), ustekinumab (1 patient), and azathioprine monotherapy (12 patients). A Rutgeerts score of i2 or higher was found in 13 patients after a median of 9 months post-surgery, with an average follow-up of 3 years Group 2 (17 patients) had an average age of 38 years, with 64.7% being active smokers. Postoperative colonoscopy was performed after a median delay of 8 months. A Rutgeerts score of i2 or higher was found in 10 patients. The treatments initiated after colonoscopy were as follows: infliximab (3 patients), infliximab-azathioprine combination (2 patients), adalimumab (7 patients), azathioprine monotherapy (4 patients), and ustekinumab (1 patient). The average follow-up after surgery was 3 years No significant differences were observed between the groups in terms of endoscopic or severe endoscopic recurrence, or clinical recurrence at 6 and 24 months post-surgery Conclusion In our study, early initiation of prophylactic postoperative treatment for patients with a single risk factor did not reduce clinical or endoscopic recurrence rates. This suggests that avoiding such early treatment could help prevent unnecessary exposure to immunosuppressants and biologics, thereby reducing risks of side effects and high costs

Predicting Postoperative Infection After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with Splenectomy.

Hematologic changes after splenectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) can complicate postoperative assessment of infection. This study aimed to develop a machine-learning model to predict postoperative infection after cytoreductive surgery (CRS) and HIPEC with splenectomy. The study enrolled patients in the national TriNetX database and at the Johns Hopkins Hospital (JHH) who underwent splenectomy during CRS/HIPEC from 2010 to 2024. Demographics, comorbidities, vital signs, daily laboratory values, and documented infections were collected. The patients were divided into infected and non-infected cohorts within 14 days postoperatively. Extreme gradient boost (XGBoost) machine-learning was used to predict postoperative infection. An initial model was generated using the TriNetX dataset and externally validated in the JHH cohort. From TriNetX, 1016 patients were included: 802 in the non-infected group (79%) and 214 (21%) in the postoperative infection group. The mean age was 61 ± 13 years, and 597 (56%) of the patientswere female. Most of the patients underwent CRS/HIPEC with splenectomy for appendiceal cancer (n = 590, 56%), followed by colorectal malignancy (n = 299, 29%). The remainder (n = 127, 15%) underwent CRS/HIPEC with splenectomy for gastric, pancreatic, ovarian, and small bowel malignancies or peritoneal mesothelioma. In detecting any infection, XGBoost exhibited excellent prediction accuracy (area under the receiver operating characteristic curve [AUC], 0.910 ± 0.073; F1 score, 0.915 ± 0.040) and retained high accuracy upon external validation with 96 demographically similar JHH patients (AUC, 0.823 ± 0.08; F1 score, 0.864 ± 0.03). A novel machine-learning algorithm was developed to predict postoperative infection after CRS/HIPEC with splenectomy that could aid in the early diagnosis and initiation of treatment.

P1117 A 24-year, single-centre perianal fistulizing Crohn’s disease cohort: documentation of demographics and factors influencing clinical and radiological remission

Abstract Background Radiological remission (RR), is the ultimate treatment goal in treatment of complex perianal fistula (cPAF) in Crohn’s disease (CD). In this study, we analysed cPAF disease characteristics and RR-related factors in a CD cohort. Methods Patients with CD (1999–2023) and MRI-confirmed cPAF (per AGA 2003 criteria, reviewed by 4 radiologists) were analyzed. Clinical remission (CR) was defined as no drainage under compression for ≥3 months, and RR as fibrotic fistula closure. Results Among 1688 CD patients, PAF prevalence was 24.7% (n=417), with 19% (n=79) classified as simple fistulas. Detailed analysis included 223 cPAF patients with sufficient follow-up. Male predominance was noted (65.5%), with a median CD diagnosis age of 28(IQR: 20) years and cPAF onset at 8(53) months. Median follow-up was 58(79) months. Isolated PAF occurred in 8.5%. Patients had a median of 2 fistulas, with ≥1 fistula in 51.6%. Common cPAF types were ISF (77%) and TSF (46%), with branching formation evident in 38.6%. Immunomodulator (IM) use was 94%, Anti-TNF+IM combination 87%, and multiple Anti-TNF exposure 35%. IFX was given to 31.8% at 5mg/8w and 51.9% at higher doses (up to 15mg/kg/4w). CR was achieved in 71% and RR in 43.5% of patients following a stepwise treatment approach including antibiotics, IM, Anti-TNF dose escalation, and diverting stoma (Figure 1). In the RR group, cPAF onset after CD diagnosis, non-mucosal (B2-B3) involvement, and abscess-related low fistulas were more frequent, while multiple cPAF, branching formation, and TSF were more common in the non-RR group (Table 1). Time-dependent analyses showed better RR associated with cPAF onset after CD diagnosis (log-rank <0.001), fewer fistulas (LR=0.035), abscess-related low fistulas (LR<0.001), and early Anti-TNF initiation (<0.008). Poor RR was linked to branched fistulas (LR=0.003), TSF (LR=0.042), and multiple Anti-TNF exposure (LR=0.017). The development of cPAF after CD diagnosis during follow-up, fistulas other than TSF, the absence multiple Anti-TNF exposure, and early initiation of Anti-TNF treatment were independently associated with better RR rates in multivariate analyses. Conclusion With a appropriate stepwise approach, including dose adjustments and stoma, RR can be achieved in 43.5% of cPAF patients. TSF-type fistulas are associated with poorer outcomes, while low perianal fistulas complicated by abscesses show better prognosis. Multiple Anti-TNF exposure predicts a poor response, whereas cPAF onset during follow-up and early Anti-TNF initiation are strongly associated with achieving RR.

Thrombopenia and hemolytic anemia in acute and emergency medicine : Detailed view at thrombotic microangiopathies

Recognizing anemia and thrombpenia in acute and emergency medicine is easy. Acute (microangiopathic hemolytic) anemia and thrombopenia can be asign of thrombotic microangiopathy (TMA). TMA syndromes are potentially life-threatening diseases. Diagnosing aTMA syndrome, causal differentiation and treatment require specialist knowledge that is not always available in acute and emergency medicine. Many differential diagnoses and examinations are usually necessary to make acorrect diagnosis. Therefore, astandardized diagnostic algorithm is helpful for early diagnosis and treatment initiation.

POEMS Syndrome.

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, Skin changes) is a syndrome that involves a monoclonal B-cell proliferation, most often plasmacytic, and a variable number of manifestations listed or not in the acronym. These manifestations include sclerotic bone lesions, plasmacytic Castleman disease, papillary edema, peripheral edema, ascites, thrombocytosis and/or polycythemia, venous and/or arterial thrombosis, and renal, pulmonary, and cardiac impairments [1]. Diagnosis is often delayed due to the rarity of this entity and its clinical polymorphism, which can mimic other neurological disorders. First-line treatment for patients without bone marrow involvement and with a limited number of bone lesions is radiation. Patients with diffuse bone lesions or bone marrow involvement should receive systemic treatment, ideally intensive treatment with autologous stem cell transplantation (ASCT) when possible. Lenalidomide and bortezomib appear to be very promising, showing very rapid efficacy on neuropathy. Early initiation of treatment, before the development of severe neurological damage, along with supportive care, especially physiotherapy, is crucial for optimal neurological recovery.

Multiple sclerosis: peculiarities of providing high-quality medical care to patients in the realities of Ukraine

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system, which is one of the most common causes of progressive disability among young people. This disease significantly affects the quality of life of patients and their families and is also accompanied by significant economic costs. Early diagnosis and early initiation of treatment of patients with MS help prevent the development of exacerbations, disability, premature death and improve quality of life. Today, awareness of MS has increased, more effective methods of diagnosis and therapy of patients with MS have become available. This has led to a reduction in the diagnostic delay between the detection of symptoms and making a reliable diagnosis, as well as to the postponement of severe disability. Multidisciplinary co-operation of specialists at all levels of medical care and close co-operation between the doctor and the patient is essential for optimal clinical management. The article systematizes current know-ledge on the main approaches to the diagnosis and treatment of patients with MS in Ukraine.

NORSE secondary to anti-GAD65 antibody-positive encephalitis treated with novel adjunctive rapid titrationVNS protocol.

New Onset Refractory Status Epilepticus (NORSE) is a rare and severe condition characterized by refractory seizures in individuals without a prior history of epilepsy. This case report describes a 37-year-old woman diagnosed with anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody-positive encephalitis-related NORSE. Her seizures were refractory to multiple interventions, including anti-seizure medications, anesthetics, immunotherapies, a ketogenic diet, and electroconvulsive therapy. Seizures recurred twice during the tapering of anesthetic medications. However, after 32 days of treatment, the seizures were successfully controlled. To maintain seizure control and facilitate the weaning of anesthetics, a Vagus Nerve Stimulator (VNS) was implanted using a novel rapid titration protocol. This allowed for the successful tapering of anesthetics by day 50, with no recurrence of seizures. At her 9-month follow-up, the patient remained seizure-free and had an improved quality of life. This case highlights that early initiation of immunosuppressive treatment may lead to a favorable prognosis. The novel application of VNS therapy assisted seizure control in NORSE, thus encouraging further research investigating the potential role of VNS in this condition. PLAIN LANGUAGE SUMMARY: New Onset Refractory Status Epilepticus (NORSE) is a rare and severe condition characterized by relentless seizures in individuals without a prior epilepsy history. This report shares the case of a 37-year-old woman with NORSE, associated with a high anti-glutamic acid decarboxylase 65 antibody titer. Her seizures were super-refractory, requiring multiple anti-seizure medications, anesthetics, immunotherapies, a ketogenic diet, and electroconvulsive therapy. Seizures recurred twice during the tapering of anesthetic medications. However, by hospital day 32, the seizures were successfully controlled with these interventions. To further stabilize seizure control and enable the successful discontinuation of anesthetics, a Vagus Nerve Stimulator (VNS) was implanted. The patient had no further seizures and gradually recovered back to her pre-disease baseline. This case suggests that a novel rapid VNS titration protocol could be a promising treatment option for NORSE, warranting further investigation.

Fever in the Trauma Bay: A Marker for Greater Risk of Adverse Outcomes.

Purpose: Previous work identified a sub-group of trauma patients at risk for bacteremia who presented with signs of infection, including fever. A majority were older adult falls who had early onset bacteremia. Hypothesis: Fever in the trauma bay is associated with a greater risk of adverse outcomes and identifies patients who might benefit from early initiation of interventions for sepsis. Methods: Trauma patients ≥18 years, drawn from a system-wide electronic medical record (EMR) (2017-2020), were included. Fever+ patients (temperature >38°C) were compared with Fever- patients (36°C-38°C). Multi-variable logistic regressions assessed the association of fever status with outcomes. The interaction between fever, age, and outcomes was assessed. Results: A total of 140,647 patients were included from 89 centers. Eight hundred ninety (0.6%) were Fever+ and had worse unadjusted outcomes. After adjustment, Fever+ patients had significantly greater mortality (adjusted odds ratios [aOR], 95% confidence interval: 1.05 [1.04-1.07]), intensive care unit use (1.08 [1.04-1.11]), and ventilator use (1.11 [1.09-1.13]). Fever+ status was associated with a significantly larger aOR of severe sepsis in older versus younger patients (≥65 y: 1.12 [1.11-1.13]; <65 y: 1.04 [1.03-1.05]). Fever+ status was also associated with a significantly larger aOR of bacteremia in older versus younger patients (≥65 y: 1.09 [1.08-1.10]; <65 y: 1.04 [1.03-1.05]). Implications: Although uncommon, fever at presentation is an ominous sign for trauma patients and portends significantly greater risks for bacteremia, sepsis, and mortality. These risks increase with age. These findings suggest older adults who present with fever warrant early aggressive intervention and may sustain injury as a consequence of debility from systemic infection.

Completed suicide risk factors among people living with HIV in Hunan Province identified through a psychological autopsy case–control study

Accumulating evidence has shown an increased risk of suicide among people living with HIV/AIDS (PLWHA). However, few studies have explored the risk factors associated with completed suicide among PLWHA. This study aimed to identify the characteristics and causes of completed suicide among PLWHA to guide future targeted suicide prevention and intervention programs. A 1:1 matched case–control psychological autopsy study was conducted among PLWHA in Hunan Province. We recruited 63 PLWHA who died by suicide from January 1, 2013, to December 31, 2019, and 63 living controls matched for age, gender, and employment. Two informants for each participant were interviewed to collect data on participants’ sociodemographic characteristics, depressive symptoms, HIV-related stress, hopelessness, and social support. The median survival time from HIV diagnosis to completed suicide was 3.9 months (IQR: 0.57–14.13). Most completed suicides occurred within six months of HIV diagnosis (71.4%), with poisoning (34.9%) and hanging (22.2%) as the primary methods. After controlling for confounding factors, we identified four risk factors of completed suicide: not receiving antiretroviral treatment (OR = 6.805; 95% CI: 1.227 to 37.738), receiving low-income subsidy (OR = 16.272; 95% CI: 3.245 to 81.598), HIV-related stress (OR = 1.332; 95% CI: 1.089 to 1.629), and hopelessness (OR = 2.910; 95% CI: 1.378 to 6.144). PLWHA are at a high risk of suicide within the first six months of HIV diagnosis, indicating an urgent need for immediate suicide screening and timely intervention. Suicide risk is affected by multiple factors, including sociodemographic, clinical, and psychological factors, indicating the need for a multifactorial approach to suicide prevention, which may involve early initiation of ART treatment and provision of economic and psychosocial support.

A Predictive Level of C-peptide for Glutamic Acid Decarboxylase Antibody Positivity in Autoimmune Diabetes

Objective: Diabetes mellitus (DM) is one of the most prevalent chronic diseases and is considered a universal health issue. This study aimed to establish a C-peptide cut-off level to predict glutamic acid decarboxylase antibody 65 (GADA) positivity in autoimmune diabetes. Methods: Designed as a retrospective methodological study, the study reviewed diabetic patients aged over 16 years who presented to adult internal medicine outpatient clinics between 2008 and 2022. The data were collected retrospectively from the hospital records. Patients were categorized into two groups according to GADA positivity, and their sensitivity and specificity were calculated for fasting C-peptide levels. Results: GADA positivity was observed in 96 of a total of 343 patients. The group with antibody positivity was younger (p &lt; .001), had lower C-peptide levels (p &lt; .001) and higher HbA1c levels (p = .03). Thyroid antibody positivity was more common in this group (p = .009). Sensitivity was 80.2% and specificity was 72.5% for the optimal C-peptide level cut-off point of ≤ 1.35 ng/mL, which predicted GADA positivity. Conclusion: GADA positivity was highly prevalent at a fasting C-peptide level cut-off point of ≤1.35 ng/mL. Hence, in clinical practice, GADA could be routinely examined in patients with a value below this level for accurate diagnosis and early initiation of treatment in autoimmune diabetes.

High-Pressure Injection Injury of the Hand-A Rare but True Surgical Emergency.

Background/Objectives: The aim is to bring attention to the existence of a rare type of trauma of the hand, high-pressure injection injury, that appears to be minor with negligible signs and symptoms within the first hours after the accident, but in reality, produces significant tissue destruction with severe consequences. Recognizing this type of trauma by medical personnel, understanding the mechanisms involved, and knowing the etiological and prognostic factors can lead to early treatment initiation and avoid severe mutilating sequelae. Methods: A retrospective study on 16 patients diagnosed with high-pressure injection injuries, including water, air, paint, paint mixed paint with thinner, petroleum jelly, and lime (washable paint containing calcium oxide). The patients' epidemiological data, the time from accident to diagnosis, reasons for delayed diagnosis, treatments applied, and outcomes were recorded and evaluated. Results: All injuries occurred at the workplace due to negligence. Oil-based paint was implicated in 31.25% of cases. The most frequently affected anatomical region was the volar surface of the distal phalanx of the nondominant hand index finger. In one case, delayed presentation to medical care and diagnosis resulted in a compartment syndrome, requiring amputation. Conclusions: It is crucial to recognize and understand this type of trauma, as it constitutes an emergency due to its rapid progression. Delayed diagnosis can result in massive tissue destruction, potentially leading to the loss of limb segments and debilitating functional sequelae, which may severely impact a patient's socio-professional life.

From stroke to depression: The need for systematic screening for post-stroke depression.

Post-stroke depression (PSD) negatively impacts the physical and mental well-being of stroke survivors. However, data on the prevalence and risk factors of PSD in African countries such as Cameroon are limited. This study aims to determine the prevalence and factors associated with PSD among stroke survivors at a hospital in Cameroon and inform clinical practice. The study was carried out in the Nkwen Baptist Hospital in the North West region of Cameroon. This was a hospital-based cross-sectional study. Stroke patients were systematically screened for PSD using the patient health questionnaire (PHQ-9). PSD was present if a patient scored ≥ 4 points on the scale. The multidimensional scale of perceived social support was used to assess the level of social support, the modified Rankin tool and Barthel index were used to assess functional independence, and the Fatigue assessment tool was used to assess post-stroke fatigue. A multivariate analysis was performed to identify factors associated with PSD. A total of 103 patients were included in the study. The mean age was 55.55 ± 12.15. Most patients were males (58.25%). The mean depression score was 5.17 ± 6.26. The overall prevalence of PSD was 36.89%. A higher functional impairment, post-stroke fatigue, perceived social support, recent stroke and being divorced were all associated with high PSD scores. In this study, we found a high prevalence of PSD using a systematic screening approach, suggesting that systematic screening for PSD can lead to early detection and management. Systematic screening for PSD in stroke patients can lead to early diagnosis and, consequently, early initiation of treatment. Integration of mental health support and care as part of the routine stroke is warranted.

International Validation of Echocardiographic AI Amyloid Detection Algorithm.

Diagnosis of cardiac amyloidosis (CA) is often missed or delayed due to confusion with other causes of increased left ventricular wall thickness. Conventional transthoracic echocardiographic measurements like global longitudinal strain (GLS) has shown promise in distinguishing CA, but with limited specificity. We conducted a study to investigate the performance of a computer vision detection algorithm in across multiple international sites. EchoNet-LVH is a computer vision deep learning algorithm for the detection of cardiac amyloidosis based on parasternal long axis and apical-4-chamber view videos. We conducted a multi-site retrospective case-control study evaluating EchoNet-LVH's ability to distinguish between the echocardiogram studies of CA patients and controls. We reported discrimination performance with area under the receiver operating characteristic curve (AUC) and associated sensitivity, specificity, and positive predictive value at the pre-specified threshold. EchoNet-LVH had an AUC of 0.896 (95% CI 0.875 - 0.916). At pre-specified model threshold, EchoNet-LVH had a sensitivity of 0.644 (95% CI 0.601 - 0.685), specificity of 0.988 (0.978 - 0.994), positive predictive value of 0.968 (95% CI 0.944 - 0.984), and negative predictive value of 0.828 (95% CI 0.804 - 0.850). There was minimal heterogeneity in performance by site, race, sex, age, BMI, CA subtype, or ultrasound manufacturer. EchoNet-LVH can assist with earlier and accurate diagnosis of CA. As CA is a rare disease, EchoNet-LVH is highly specific in order to maximize positive predictive value. Further work will assess whether early diagnosis results in earlier initiation of treatment in this underserved population.

Practical Recommendations for the Diagnosis and Management of Lysosomal Acid Lipase Deficiency with a Focus on Wolman Disease.

Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease with two distinct phenotypes, an infantile-onset form (formerly Wolman disease) and a later-onset form (formerly cholesteryl ester storage disease). The objective of this narrative review is to examine the most important aspects of the diagnosis and treatment of LAL-D and to provide practical expert recommendations. The infantile-onset form occurs in the first weeks of life and is characterized by malnourishment and failure to thrive due to gastrointestinal impairment (vomiting, diarrhea, malabsorption), as well as systemic inflammation, hepatosplenomegaly, and adrenal calcifications. Mortality is close to 100% before one year of life in the absence of specific treatment. The later-onset form can be diagnosed in childhood or adulthood and is characterized by chronic liver injury and/or lipid profile alterations. When LAL-D is suspected, enzyme activity should be determined to confirm the diagnosis, with analysis from a dried blood spot sample being the quickest and most reliable method. In infantile-onset LAL-D, the initiation of enzyme replacement therapy (sebelipase α) and careful nutritional management with a low-lipid diet is very urgent, as prognosis is directly linked to the early initiation of specific treatment. In recent years, our knowledge of the management of LAL-D has increased considerably, with improvements regarding the initial enzyme replacement therapy dose and careful nutritional treatment with a low-lipid diet to decrease lipid deposition and systemic inflammation, leading to better outcomes. In this narrative review we offer a quick guide for the initial management of infantile-onset LAL-D.

Right coronary artery pericoronary fat attenuation index as a future predictor for acute coronary events in nonobstructive coronary artery disease - a prospective single centre study.

Evaluation of pericoronary adipose tissue changes induced by inflammation by non-invasive techniques is challenging. To find the association between pericoronary adipose tissue attenuation (FAI) changes and future acute coronary events in nonobstructive coronary artery disease. Ours was a single-centre, prospective observational study on patients with atypical chest pain who underwent coronary computed tomography angiography (CCTA). In patients with CADRADS 1 to 3 nonobstructive coronary artery disease (CAD), pericoronary FAI was measured around the proximal right coronary artery (RCA) and coronary artery segment with plaque using semi-automated postprocessing software. Patients were followed up for development of acute coronary events (ACE). Kaplan-Meier curves were used to see event-free survival rates. Of 120 patients with a mean follow-up period of 67 months, 21 patients developed acute coronary events. RCA-FAI and lesion FAI of patients with ACE were significantly higher as compared to patients without events. ROC curve analysis showed RCA-FAI as the best predictor of ACE at a cut-off point of>-77.3 Hounsfield unit (HU) (with an AUC of 0.915) with high sensitivity (95.24%), specificity (83.84%), and negative predictive value (98.80%). On multivariate analysis, RCA-FAI, diabetes mellitus, and stenosis ≥50% were independent risk factors of ACE with hazard ratios of 1.335 (1.173-1.518), 4.950 (1.716-14.278), and 7.446 (2.257-24.566), respectively. RCA FAI can predict ACE in nonobstructive coronary artery disease patients. Detection of high RCA FAI of>-77.3 HU on CCTA can help to identify high-risk patients who need regular follow-up and early initiation of interventions.

Acute mitral regurgitation causing right-sided pulmonary edema: a case report

A young female presented to our emergency department with sudden-onset shortness of breath and orthopnea. Her condition rapidly worsened. She developed severe respiratory failure and cardiogenic shock ensued. Noticeably, the patient's CT scan showed a unique pattern of right-sided unilateral pulmonary edema, a feature highly specific for severe mitral regurgitation. Echocardiography confirmed papillary muscle rupture and acute mitral valve prolapse to be the cause. Her condition improved significantly after mitral valve replacement and with respiratory and circulatory support, as well as with other heart failure treatment. The classic symptoms of acute left heart failure combined with the unique CT manifestation of predominantly right-sided pulmonary edema suggested severe mitral regurgitation. Prompt diagnosis and early initiation of treatment aimed at the underlying cause is of great significance in improving the patient's prognosis.

Glaucoma Progression in Treatment-Naïve Patients With Normal Tension Glaucoma With Myopia-Role of Intraocular Pressure.

While myopia has been recognized as a positive prognostic factor for normal tension glaucoma (NTG) progression in the adult population, some myopic NTG eyes exhibited significant progression within 2 years when left untreated, even under low intraocular pressure (IOP). To determine the natural history and risk factors associated with progressive retinal nerve fiber layer (RNFL) thinning in previously stable, treatment-naïve, patients with NTG with myopia. This study included 111 myopic NTG eyes without IOP-lowering treatment for at least 1 year and without disease progression during the treatment-free period. The RNFL thickness was measured, and a visual field test was performed every 6-12 months for >2 years. Patients with progressive changes were classified as the P(+) group, whereas those without progression were classified as the P(-) group. Cox proportional hazards model assessed risk factors of progression, whereas linear regression determined factors associated with the rate of RNFL thinning. Progressive change was observed in 25 of the 111 participants [P(+) group, 22.5%]. A family history of glaucoma, higher mean IOP, and maximum IOP during the follow-up were significant factors both for being in the P(+) group and for a faster RNFL thinning. None with a mean IOP <11 mm Hg were in the P(+) group. Davies test identified that 14.2mm Hg was a significant breakpoint ( P = 0.042), above which the rate of RNFL thinning increased significantly with the mean IOP ( R2 = 0.252, P = 0.034). Patients with myopic NTG untreated for IOP, especially those with a family history of glaucoma or higher IOP, are at increased risk of progression. Early treatment initiation is advised for high-risk patients with myopic NTG, even when their condition appears stable.

Determinants of long-term disability in chronic inflammatory demyelinating polyradiculoneuropathy: A multicenter Korea/UK study of 144 patients.

Despite standard-of-care treatment, therapeutic outcomes in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are often incomplete. We aimed to evaluate the impact of clinical and therapeutic factors on long-term disability in CIDP, from cohorts from Korea and the UK. We conducted a retrospective multicenter cohort study of 144 patients with CIDP. Baseline characteristics and treatment data were collected, and disability was assessed using the Overall Neuropathy Limitation Scale (ONLS) for the UK cohort, Inflammatory Neuropathy Cause and Treatment (INCAT) scores for the Korean cohort, and Inflammatory Rasch-built Overall Disability Scale (I-RODS) for the combined cohort. Univariate and multivariate linear regression analyses were performed to identify independent prognostic factors. Subgroup analyses were conducted according to important clinical features to gain further insights into which patients are most likely to benefit from early treatment. Treatment initiation within 1 year of onset was significantly associated with lesser post-treatment disability and greater amplitude of treatment response, in each cohort separately, and in the combined cohort. This association remained significant after adjusting for covariates in multivariate regression. Subgroup analyses demonstrated early treatment benefits in older patients (≥60 years), those with typical CIDP, and those with a chronic mode of onset. The type of first-line therapy and baseline disability levels did not influence outcomes. Other identified independent prognostic factors included comorbidity and pre-treatment disability level. Early treatment initiation is a key modifiable determinant of favorable long-term disability in CIDP. These findings underscore the importance of timely diagnosis and prompt treatment to prevent irreversible axonal damage.