Disease Entity Research Articles

Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called “other oncocytic tumors”, namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.

A Young Man With Hereditary Motor And Sensory Neuropathy: A Rare Genetic Association

Hereditary motor and sensory neuropathies with early onset are uncommon conditions that include Dejerine-Sottas neuropathy, which begins in infancy, and congenital hypomyelinating neuropathy, which manifests in the early postnatal period. However, these two historically defined disease entities are only small parts of the clinical spectrum. It is well recognized that very early onset hereditary neuropathies are frequently caused by de novo dominant mutations in PMP22, MPZ, and EGR2. In addition, mutations in several other dominant and recessive genes for Charcot-Marie-Tooth disease may lead to similar phenotypes. A 20-year-old boy had complaints of weakness of both lower limbs for 1 year, followed by wasting and foot drop, which subsequently involved the upper limbs. Nerve conduction velocity and electromyography of both lower limbs revealed demyelinating sensory motor polyneuropathy. Histological examination of the sural nerve revealed a nerve trunk with perineural soft tissue, with the nerve bundles being irregular and separated by fibrous tissue bands. The later reveals small perivascular infiltration of chronic inflammatory cells, and no granuloma or AFB is seen. The genetic test of whole exome screening for heriditatory neuropathy showed pathogenic (PM2, PVS, PP5) with a gene impact of (NF2: c.363+1G>T), which is a rare entity in our case study to consider the diagnosis despite negative family history. We highlight this rare disease in young man with a high index of clinical suspicion for its diagnosis. Bangladesh J Medicine 2024; 35: 101-105

New drugs for the treatment of hyperlipidemia in statin-intolerant patients - review

Introduction Cardiovascular diseases are the most numerous group of diseases prevalent in the world. They are a challenge for many health systems, in terms of keeping life comfortable and also economics. The cause of selected disease entities is too much cholesterol in the blood. The most popular treatment for hypercholesterolemia is based on statins. Many patients are affected by intolerance to these drugs, so an important issue is the discovery and improvement of alternatives to statins. Purpose of work The purpose of this review is to collect literature data on the latest treatments for hypercholesterolemia with drugs other than statins and ezetimibe. Materials and methods Materials are from a review of recent literature available in PubMed. To search for articles, we used keywords such as: bempedoic acid, non-statin therapy, cardiovascular risk, inclisiran, alirocumab, cardiovascular disease, dyslipidemia, evolocumab. Summary Treatment of hypercholesterolemia with statins remains the most popular management strategy. Intolerance to treatment with these drugs creates serious clinical problems for patients. Recently, we could see the emergence of new drugs as alternatives to statins. As the results show, the new drugs can effectively replace statins in the hypolipemic treatment especially of patients who cannot be treated with them.

Independent predictors of MACE in patients with cancer

Abstract Funding Acknowledgements None. Background/Introduction Cardiovascular disease and cancer are the leading causes of death worldwide. Both disease entities share common risk factors. More importantly, the main cause of death after disease progression is cardiovascular disease in patients with cancer. Despite the recent advancements in the field of cardio-oncology, the main prognostic factors of major adverse cardiovascular events (MACE) remain elusive. Purpose To investigate prognostic factors of MACE in a single center cardio-oncology registry. Methods Consecutive patients referred to the cardio-oncology outpatient clinic of a tertiary center for cardiologic consultation were included. All patients were followed up clinically or by telephone. Data from national records were also used. Results In total, 115 patients were included in the analysis. Of them, 60 (52.2%) were female and the majority of study population suffered from breast cancer (27%). Thirteen patients (11.3%) had hematologic malignancies and the rest solid tumors. Chemotherapy was received by a total of 94 patients (81,7%). The mean follow -up duration was 446 days. During follow up, 32 MACEs (27.8%) occurred. Death from any cause occurred in 21 patients (including 2 cardiac deaths), hospitalization due to heart failure in 6, myocardial infarction in 2, pulmonary embolism in 3 and stroke in 1 patient. In multivariate logistic regression analysis, diabetes mellitus was an independent predictor of MACE, after adjustment for cardiovascular risk factors and body mass index (OR=3.37, 95% CI 1.14-9.99). In Kaplan Meier plots patients with diabetes mellitus showed higher incidence of MACE (log rank p=0.03). Conclusions In the present single center study, diabetes mellitus emerged as an independent predictor of MACE. This finding confirms the important and primary role of cardio-oncology units in the strict management of cardiovascular risk factors, leading to improved prognosis of this patient-population.Kaplan Meier Curve

Review on Role of Yoga in Chittodvega w.s.r. to Generalized Anxiety Disorder

Mental health disorders are mentioned as 3rd health burden in India according to WHO survey. Generalized anxiety disorders are a chronic anxiety disorder characterized by excessive and uncontrollable worry and anxiety about everyday life events and situations. In Ayurveda many psychological disorders are mentioned in Samhitas. Terms like Asvastha Chitta, Chittavimbhramsa, Chittodvega etc. seems similar to Generalized anxiety disorder, however Chittodvega seems to be nearest correlation for this disease entity. Acharya Charaka has listed Chittodvega as Manas Dosha Vikara. People with symptoms of Generalized anxiety disorder always tend to expect failure and can't stop worrying, Clinical trials have shown that anxiolytic drugs alone have limited long-term efficacy. Moreover, they often have adverse side effects including dependency, drowsiness, impaired cognition and memory and sexual dysfunction. Being an alarming disease GAD needs an effective management. Nowadays Yoga is considered as a popular approach to improve emotional health. Yoga, a form of holistic mind–body medicine, that includes the use of physical postures (Asanas), breathing practices (Pranayamas), meditations, relaxation techniques and lifestyle changes based on ancient yogic philosophy. Pranayama should be practiced to remove the blockages and to lift you out of the Tamasik and Rajasik states. Asanas empathizes physical strength and helps to maintain balance between mind and body. Yoga helps to restraint unnecessary mental fluctuations and thus helps in stabilizing and calming the mind. Thus it might be an effective and safe intervention for individuals with GAD.

Management of Hridroga (CVD’S)

Hridraya is an epitome of sustenance and co-ordination to maintain Ayu. It is considered as one of the three Marma sthana, and is the seat of Sarira, Buddhi, Indriya, Indriyartha, Saguna atma, Mana, etc so, any deviation in its functioning can be tremendously bereaving. Acharya Charaka, Sushruta, Vagbhata and Bhela have been unanimous regarding Hridaya being the seat of Manas and Buddhi. Hridroga is an ocean full of disease entities. In contemporary medical system, it is known as CVD i.e., Cardio-Vascular Disease. CVDs are the leading cause of death taking an estimated 17.9 million lives in 2019 accounting for whooping 32% of all the global deaths. Most cardiovascular diseases can be prevented by addressing behavioural risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity and harmful use of alcohol. These risk factors can be effectively tackled by the judicious adherence to Dinacharya, Ratricharya, Ritucharya, Sadvritta niyamas, etc. Even in the state of disease, compliance with Sodhana procedures and Oushadhas can lead to alleviation of disease and qualitative improvement in the state of Ayu. This article gives 360° view of Shaman oushadhas related to Hridroga, which is explained by the Apta in various ancient texts.

High frequency of BCP, but less CPP crystal-mediated calcification in cartilage and synovial membrane of osteoarthritis patients

ObjectiveEctopic articular calcification is a common phenomenon of osteoarthritic joints, and closely related with disease progression. Identification of the involved calcium crystal types represents an important topic in research and clinical practice. Difficulties in accurate detection and crystal type identification have led to inconsistent data on the prevalence and spatial distribution of BCP and CPP deposition. MethodCombining multiple imaging methods including conventional radiography, histology and Raman spectroscopy, this study provides a comprehensive analysis of BCP and CPP based calcification, its frequency and distribution in cartilage and synovial membrane samples of 92 OA patients undergoing knee replacement surgery. ResultsConventional radiography showed calcifications in 35% of patients. Von Kossa staining detected calcified deposits in 88% and 57% of cartilage and synovial samples, respectively. BCP crystals presented as brittle deposits on top of the cartilage surface or embedded in synovial tissue. CPP deposits appeared as larger granular needle-shaped clusters or dense circular pockets below the cartilage surface or within synovial tissue. Spectroscopic analysis detected BCP crystals in 75% of cartilage and 43% of synovial samples. CPP deposition was only detected in 18% of cartilage and 15% of synovial samples, often coinciding with BCP deposits. ConclusionBCP is the predominant crystal type in calcified cartilage and synovium while CPP deposition is rare, often coinciding with BCP. Distinct and qualitative information on BCP and CPP deposits in joint tissues give rise to the speculation that different disease entities are involved that might need different treatment strategies.

Blood parameters in pediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

Patients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) clinically present e.g. with acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM) or aquaporin-4-IgG (AQP4-IgG) negative neuromyelitis optica spectrum disorders (NMOSD)-like phenotypes. We aimed to analyze and compare blood parameters in children with MOGAD, AQP4-IgG-positive NMOSD (hence NMOSD), multiple sclerosis (MS) and healthy controls (HC). We evaluated differences in complete blood counts (CBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and C-reactive protein (CRP) between these four groups and within the groups between clinical attack, acute treatment and remission. Our cohort consisted of 174 children and adolescents with a total of 550 timepoints: 66 patients had MOGAD (202 timepoints), 11 NMOSD (76 timepoints), 58 MS (219 timepoints) and 39 were HC (53 timepoints). At clinical attack, leukocyte counts were elevated in MOGAD compared to remission (p<0.001) and compared to all other groups (p<0.001). NLR was high in MOGAD and NMOSD, and PLR was high in NMOSD, however, after correction for multiple testing these findings did not remain significant. While glucocorticoids caused an increase of leukocyte counts and NLR in NMOSD and MS, these values remained stable during acute treatment in MOGAD. In remission, NLR normalized in MOGAD, while it stayed high in NMOSD. PLR increased in NMOSD and was significantly higher compared to all other groups. Some blood parameters, mainly leukocyte and differential counts, might help clinicians to evaluate disease activity, differentiate relapses from pseudo-relapses and even distinguish between different disease entities.

Variation in neuroimaging and outcomes in patients with Sturge Weber syndrome Type III

ObjectivesSturge Weber syndrome (SWS) is a neurovascular condition with an estimated incidence of 1 in 20,000 to 50,000 live births. SWS Types I and II involve cutaneous and ophthalmological findings, with neurological involvement in Type I. SWS Type III is exclusive to brain stigmata. Our study aims to describe the characteristics of brain MRI findings and report neuroradiological features with seizure and cognitive outcomes in patients with SWS Type III. MethodsThis is a retrospective case series examining the clinical, radiological, and cognitive characteristics of patients with SWS Type III referred to the SWS Clinic at Boston Children’s Hospital. We analyzed brain MRI findings based on vascular and parenchymal features. Clinical and cognitive outcomes were based on a validated assessment tool in this population (Neuroscore). ResultsThis dedicated case series of patients with Type III SWS from a single center identified ten patients. All patients had classic stigmata indicative of SWS. Two distinct radiological phenotypes were found, one characterized by more pronounced deep venous enlargement, and the other, with more pronounced parenchymal abnormalities. There was heterogeneity in seizure presentation and outcome. Earlier age of onset and seizures predict more severe outcomes, as seen in classic SWS. ConclusionWe could not find significant divergence in outcomes between patients with differing neuroimaging phenotypes. These results raise the question of whether the two distinct radiological phenotypes found in SWS Type III are reflective of different disease entities, with underlying genetic heterogeneity. These results suggest the need for larger, multi-center natural history studies.

An Update on H3K27M-altered Diffuse Midline Glioma: Diagnostic and Therapeutic Challenges in Clinical Practice

H3K27-altered diffuse midline glioma (DMG H3K27-altered) is a relatively newly-designated WHO entity which primarily affects the midline structures of the central nervous system (CNS), including the brainstem (predominantly pontine region), thalamus, midbrain, or spinal cord, and primarily affects children and young adults. Despite the proximity of these tumors to eloquent areas in the CNS, novel stereotactic approaches have facilitated the ability to obtain tissue diagnoses without significant morbidity, providing molecular diagnostic information in more than half of patients. Conventionally fractionated radiation therapy to a total dose of 54-60 Gy in 27-30 fractions and 24 Gy in 12 fractions play a crucial role in the definitive treatment of these tumors in the primary and salvage settings, respectively. Hypofractionated regimens may allow for accelerated treatment courses in selected patients without jeopardizing disease control or survival. The decision to add concurrent or adjuvant systemic therapy mainly relies on the physicians’ experience without solid evidence in the literature in favor of any particular regimen. Recently, novel agents, such as ONC201 have demonstrated promising response rates in progressive/recurrent tumors and are currently under investigation in ongoing randomized trials. Given the scarcity of data and well-established guidelines due to the rare nature of the disease, we provide a contemporary overview the molecular underpinnings of this disease entity, describe the role of radiotherapy and systemic therapy, and provide practice management principles based on the published literature.

Clinical complexity unveiled: A case of primary biliary cholangitis autoimmune hepatitis overlap syndrome

Overlap syndrome with primary biliary cholangitis and autoimmune hepatitis (PBC-AIH) remain uncommon liver autoimmune-related disorders. Diagnosis is based on clinical, biochemical, serological, and histological findings. Early diagnosis of the disease will give the best outcome even though evidence-proven treatment is still unavailable to tackle this disease entity. Here, we present a case of a Sri Lankan woman diagnosed with PBC-AIH overlap syndrome. She presented with symptoms of jaundice and pruritus. Extensive investigations, including liver biopsy were instrumental in confirming the diagnosis.

High levels of soluble P-selectin, neutrophil extracellular traps, and myeloperoxidase as risk factor of deep vein thrombosis in malignancy patients receiving platinum-based chemotherapy

Backgrounds Venous Thromboembolism (VTE) is a disease entity comprising Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). VTE events increase the mortality rate of patients with cancer receiving platinum-based chemotherapy. Soluble P-Selectin, Neutrophil Extracellular Traps (NET), and myeloperoxidase (MPO) are risk factors associated with DVT in malignancy patients receiving platinum-based chemotherapy. The purpose of this study was to determine the role of soluble P-selectin, NET, and MPO as risk factors for DVT in patients with malignancy receiving platinum-based chemotherapy. Patients and Methods This study used a case-control design (matched pair case-control study) based on age and gender. The case group consisted of subjects with DVT, whereas the control group consisted of subjects without DVT. The subjects were 31 in each case and control groups. Soluble P-selectin, NET, and MPO levels were measured in each group. Results The mean age of case group was 50.26±12.15 years meanwhile in control group was 52.81±11.64 years. In the case group, 71% of the subjects were female, whereas 51.6% of the control group were male. Most subjects, either in the case group (71%) or the control group (71%), used carboplatin. In the case group, cervix malignancy was the most common malignancy (32.3%), whereas in the control group, it was nasopharyngeal malignancy (25.8%). High soluble P-selectin level was a risk factor for DVT (OR 3.38, CI 1.180 – 9.780, p=0.02). A high NET level was also a risk factor for DVT (OR 2.88, CI 1.026-8.074, p=0.04). The high MPO levels in this study could not be proven as a risk factor. Conclusions Soluble P-selectin and NET are risk factors that play a role in the pathophysiology of DVT through the pathomechanism of immunothrombosis induced by endothelial injury and activation of monocytes and neutrophils due to the use of platinum-based chemotherapy.

Congenital Sternoclavicular Sinus-Case Series of a Rare Lower Neck Deformity.

We encountered patients with a congenital cutaneous sinus tract in the sternoclavicular joint region, which we designate as "congenital sternoclavicular sinus (CSCS)." The aim of this investigation is to enhance recognition of this subtle yet noteworthy entity and develop standardized protocols for its management. Between 2013 and 2023, 172 patients, including 78 males and 94 females, were referred to our institution for the management of CSCS. Clinical charts were retrospectively reviewed. The majority of patients (60.5%) were young children below 3 years of age, with only six adult patients and a median age of 27.5 months. The left side was implicated in 157 cases (91.3%). In 146 cases (84.9%), a faint skin streak was noted above the orifice. Yet, no pharyngeal sinus tracts were detected, either through barium swallow studies or direct laryngoscopy. All skin lesions featured a diminutive orifice near the sternoclavicular joint, with the tract extending deeply into the subcutaneous tissue and terminating blindly, short of entering the joint, after a distance of 10 mm (ranging from 5 to 21 mm). Histopathological analysis revealed that the epithelial lining predominantly consisted of stratified squamous epithelium (87.8%), with ciliated columnar epithelium accounting for the remaining 12.2%. CSCS, though infrequent, presents with distinctive pathological and clinical features. The condition predominantly affects the left sternoclavicular joint region, with the notable "skin streak sign" aiding in diagnosis. We considered CSCS as one disease entity of branchial arch anomalies. Complete surgical excision offers a definitive cure. 4 Laryngoscope, 2024.

Calcium Homeostasis Abnormalities in Patients Taking Chronic Anticonvulsants Therapy – A Cross-sectional Study

Introduction: Epilepsy is a well-known disease entity that is responsible for a significant amount of morbidity. The purpose of this research is to determine the frequency of calcium homeostasis abnormalities in patients who are taking chronic anticonvulsant medication and to analyze the levels of Vitamin D in the serum of patients who are taking chronic anticonvulsant medication. Materials and Methods: The SVRRGGH general medicine department in Tirupati conducted this cross-sectional single-centered prevalence study. The study included outpatients, inpatients, and acute medical care (AMC) patients. After applying the inclusion and exclusion criteria, the study randomly selected 100 seizure disorder patients from the SVRRGH in Tirupati. Epilepsy patients who participated in the study were asked about medication, compliance, and seizure control. Anticonvulsant usage and duration were recorded. Serum calcium, Vitamin D, alkaline phosphatase (ALP), and parathormone were measured. Hypoalbuminemia caused calcium adjustments. Liver and renal function tests ruled out other major causes of hypovitaminosis D. Results: In this study, 36% were hypocalcemic and 64% were normocalcemic. There was a significant association between a number of drugs, duration of up to 12 months, normal Vitamin D levels, and good seizure levels with hypocalcemia ( P &lt; 0.001). Around 25% had high ALP levels and 75% had normal ALP levels. High ALP levels were significantly associated with hypocalcemia ( P &lt; 0.001). Conclusion: Chronic anticonvulsant therapy is associated with significant hypocalcemia and hypovitaminemia D, and our findings suggest that calcium and Vitamin D supplementation might be beneficial for patients experiencing these conditions.

Ferroptosis Biology.

Ferroptosis is a regulated cell death modality triggered by iron-dependent lipid peroxidation. Ferroptosis plays a causal role in the pathophysiology of various diseases, making it a promising therapeutic target. Unlike all other cell death modalities dependent on distinct signaling cues, ferroptosis occurs when cellular antioxidative defense mechanisms fail to suppress the oxidative destruction of cellular membranes, eventually leading to cell membrane rupture. Physiologically, only two such surveillance systems are known to efficiently prevent the lipid peroxidation chain reaction by reducing (phospho)lipid hydroperoxides to their corresponding alcohols or by reducing radicals in phospholipid bilayers, thus maintaining the integrity of lipid membranes. Mechanistically, these two systems are linked to the reducing capacity of glutathione peroxidase 4 (GPX4) by consuming glutathione (GSH) on the one and ferroptosis suppressor protein 1 (FSP1, formerly AIFM2) on the other hand. Notably, the importance of ferroptosis suppression in physiological contexts has been linked to a particular vulnerability of renal tissue. In fact, early work has shown that mice genetically lacking Gpx4 rapidly succumb to acute renal failure with pathohistological features of acute tubular necrosis. Promising research attempting to implicate ferroptosis in various renal disease entities, particularly those with proximal tubular involvement, has generated a wealth of knowledge with widespread potential for clinical translation. Here, we provide a brief overview of the involvement of ferroptosis in nephrology. Our goal is to introduce this expanding field for clinically versed nephrologists in the hope of spurring future efforts to prevent ferroptosis in the pathophysiological processes of the kidney.

A comparative analysis of the clinical and genetic profiles of blast phaseBCR::ABL1-negative myeloproliferative neoplasm and acute myeloid leukemia, myelodysplasia-related.

The classic Philadelphia chromosome-negative myeloproliferative neoplasms (Ph (-) MPNs), have variable potential for progression to the blast phase (MPN-BP) of the disease. Except initiated by distinct driver mutations, MPN-BP frequently carry similar genetic abnormalities defining acute myeloid leukemia myelodysplasia-related (AML-MR). Because of dissimilar initial pathogenesis, MPN-BP and AML-MR are retained under different disease categories. To determine if separately classifying these entities is justified, we compare MPN-BP with AML-MR patients based on mutational landscape and clinical parameters. 104 MPN-BP patients and 145 AML-MR patients were identified with available clinical, cytogenetic, and genetic data. AML-MR patients presented with a higher blast count (median, 51% vs. 30%) while MPN-BP patients had higher WBC counts, platelet counts and bone marrow cellularity (all p<0.0001). Patients with MPN-BP showed similar genetic mutations with similar mutation pattern (functional domain, hotspot and locus involved by the mutations) but a different mutation rate from AML-MR, with more frequent JAK2, CALR, MPL, ASXL1, IDH2, SETBP1 and SRSF2 mutations and less frequent TP53 and DNMT3A mutations. The overall survival (OS) of MPN-BP (OS post-BP-progression) is comparable to that of AML-MR (median OS, 9.5 months vs. 13.1 months, p=0.20). In addition, the subgroups of MPN-BP show similar OS as AML-MR. When harboring certain mutation such as TP53, ASXL1, DNMT3A, TET2, RUNX1, IDH1, IDH2, EZH2, U2AF1, BCOR and SRSF2, MPN-BP and AML-MR patients carrying the same somatic mutation show no difference in OS. MPN-BP and AML-MR harbor similar somatic mutations and clinical outcomes, suggesting a unified clinical disease entity.

Fundus Autofluorescence in Posterior and Panuveitis—An Under-Estimated Imaging Technique: A Review and Case Series

Fundus autofluorescence (FAF) is a prompt and non-invasive imaging modality helpful in detecting pathological abnormalities within the retina and the choroid. This narrative review and case series provides an overview on the current application of FAF in posterior and panuveitis. The literature was reviewed for articles on lesion characteristics on FAF of specific posterior and panuveitis entities as well as benefits and limitations of FAF for diagnosing and monitoring disease. FAF characteristics are described for non-infectious and infectious uveitis forms as well as masquerade syndromes. Dependent on the uveitis entity, FAF is of diagnostic value in detecting disease and following the clinical course. Currently available FAF modalities which differ in excitation wavelengths can provide different pathological insights depending on disease entity and activity. Further studies on the comparison of FAF modalities and their individual value for uveitis diagnosis and monitoring are warranted.

Clinical Prediction Models for Prognosis of Colorectal Liver Metastases: A Comprehensive Review of Regression-Based and Machine Learning Models.

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of "high-risk" patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework.

Clinical outcomes of antithrombin III supplementation in an overt disseminated intravascular coagulation: a longitudinal single-institutional experience and retrospective analysis.

Antithrombin is a small plasma glycoprotein synthesized in the liver that belongs to the serpin family of serine protease inhibitors and inactivates several enzymes in the coagulation pathway. It plays a leading major factor on coagulation pathway, therefore administration of antithrombin is essential to treat serious clinical conditions such as disseminated intravascular coagulation (DIC). Despite the theoretical benefits of antithrombin supplementation, the optimal antithrombin activity for heparin efficacy and the benefits of antithrombin supplementation in various disease entities are not yet fully understood. The strict administration guidelines on antithrombin III in cases of DIC by the National Health Insurance Service and the Ministry of Food and Drug Safety complied as follows: antithrombin levels below 20 mg/dL in adults; antithrombin activity below 70% of normal in adults; total administration period of antithrombin must be carefully limited to within maximum 3 days, and the total administration dose must be below 7,000 international unit (IU), (loading dose, 1,000 IU in 1 hour: maintenance dose, 500 IU every 6 hours for 3 days). We identified 76 eligible for analysis according to the above-mentioned criteria in our institution (male/female, 59/17). Forty-four were identified to the non-survivor group and 32 patients were recognized as the survivor group. The baseline parameters in the non-survivor and survivor groups were comparable with no significant differences in age (66.5±18.1 vs. 66.0±16.2 years, P=0.90), sex (32/12 vs. 27/5, P=0.35), hospital length of stay (31.1±34.5 vs. 31.2±26.1 days, P=0.99), sequential organ failure assessment (SOFA) (7.3±2.5 vs. 6.6±2.0, P=0.22), simplified acute physiology score II (SAPS II) (46.0±8.8 vs. 43.5±9.2, P=0.23), cause for DIC (P=0.95), and underlying disease (P=0.38). The levels of antithrombin III on the day just before the administration significantly lower in the non-survivor groups than in the survivor groups (50.1%±13.6% vs. 57.6%±12.5%, P=0.01). The hemoglobin level in the 2nd day and 7th day after antithrombin III administration was significantly different between the non-survivor and survivor groups (9.9±1.9 vs. 11.0±2.0 g/dL, P=0.01, and 9.4±1.8 vs. 10.5±1.6 g/dL, P=0.006). The antithrombin III levels on the day of administration [area under the curve (AUC) =0.672] demonstrated significantly better prediction of mortality than the A antithrombin III levels on 1st day (AUC =0.552), the 2nd day (AUC =0.624), and 7th day (AUC =0.593). Our study suggests that the antithrombin administration may be effective tools for DIC treatment, and may be more positively considered, especially in the cases of DIC, which is a frequent complication of septic shock, sepsis, and other critical disease entities and which is associated with a high level of mortality. Furthermore, our study also suggests that the total doses and periods of antithrombin administration, which recommended by national guidelines, may be insufficient, therefore prolongation of period and increase of total dose of antithrombin supplement might be necessary.

The Dutch Idiopathic Ventricular Fibrillation Registry: progress report on the quest to identify the unidentifiable.

Idiopathic ventricular fibrillation (iVF) is arare cause of sudden cardiac arrest and, by definition, adiagnosis of exclusion. Due to the rarity of the disease, previous and current studies are limited by their retrospective design and small patient numbers. Even though the incidence of iVF has declined owing to the identification of new disease entities, an important subgroup of patients remains. To expand the existing Dutch iVF Registry into alarge nationwide cohort of patients initially diagnosed with iVF, to reveal the underlying cause of iVF in these patients, and to improve arrhythmia management. The Dutch iVF Registry includes sudden cardiac arrest survivors with an initial diagnosis of iVF. Clinical data and outcomes are collected. Outcomes include subsequent detection of adiagnosis other than 'idiopathic', arrhythmia recurrence and death. Non-invasive electrocardiographic imaging is used to investigate electropathological substrates and triggers of VF. To date, 432 patients have been included in the registry (median age at event 40years (interquartile range 28-52)), 61% male. During amedian follow-up of 6(2-12) years, 38patients (9%) received adiagnosis other than 'idiopathic'. Eleven iVF patients were characterised with electrocardiographic imaging. The Dutch iVF Registry is currently the largest of its kind worldwide. In this heterogeneous population of index patients, we aim to identify common functional denominators associated with iVF. With the implementation of non-invasive electrocardiographic imaging and other diagnostic modalities (e.g. echocardiographic deformation, cardiac magnetic resonance), we advance the possibilities to reveal pro-fibrillatory substrates.