Clinical Suspicion Research Articles

Treatment of infections caused by carbapenem-resistant Acinetobacter baumannii

Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drugs can alleviate or prevent the effects of CRAB infections, shorten hospital stays, and reduce patient mortality.

Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens: Examination of Clinical Impact.

Pulmonary thrombotic arteriopathy (PTA) can be an incidental finding in lung resections performed for various indications. Historic studies largely examined PTA in autopsies. Thus, the prevalence in surgical samples, particularly in the modern era of lung cancer screening, is poorly defined. Detection of PTA in surgical samples may provide an opportunity for therapeutic intervention, but the impact of this finding on clinical management is unknown. We retrospectively examined consecutive lung surgical resections containing a report of incidental PTA between 2019 and 2022 in our institution. A retrospective chart review was performed to determine the history of systemic thromboembolism and clinical and radiographic follow-up. All slides were reviewed to morphologically characterize the vascular changes. Among 2930 pulmonary resections, 66 (2.3%) reportedly contained PTA. Twenty-four (36.4%) patients had a clinically recognized thromboembolic event either before or after surgical resection. Patients with clinically recognized thromboembolic disease were significantly more likely to have both acute and organized thrombi affecting large arteries. The presence of infarct, chronic hypertensive vasculopathy, or number of vessels with thrombi were not significantly associated with a clinically detected event. Reporting of incidental PTA led to clinical intervention in six patients and confirmed systemic thromboembolic disease in 2. Moreover, 2 patients with no further workup based on the incidental pathology findings subsequently developed pulmonary embolism. PTA is incidentally detected in 2.3% of surgical lung resections, and in two-thirds of cases, there is no clinical suspicion of thromboembolic disease. Pathologic reporting of PTA rarely led to clinical intervention, suggesting a need for improved communication of incidental pathology findings.

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units, and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody-negative patients. We observed statistical differences between antibody-positive and -negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody-positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

18F]-florbetaben PET/CT is sensitive for cardiac AL amyloidosis.

Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.

Wernicke Encephalopathy: Typical and Atypical Findings in Alcoholics and Non-Alcoholics and Correlation with Clinical Symptoms.

Clinical diagnosis of Wernicke encephalopathy (WE) can be challenging due to incomplete presentation of the classical triad. The aim was to provide an update on the relevance of standard MRI and to put typical and atypical imaging findings into context with clinical features. In this two-center retrospective observational study, the local radiology information system was searched for consecutive patients with clinical or imaging suspicion of WE. Two independent raters evaluated T2-weighted imaging (WI), fluid-attenuation inversion recovery (FLAIR), diffusion WI (DWI), T2*WI and/or susceptibility WI (SWI), and contrast-enhanced (CE)-T1WI, and noted the involvement of typical (i.e., mammillary bodies (MB), periaqueductal grey (PAG), thalamus, hypothalamus, tectal plate) and atypical (all others) lesion sites. Unusual signal patterns like hemorrhages were also documented. Reported clinical features together with the diagnostic criteria of the latest guidelines of the European Federation of Neurological Societies (EFNS) were used to test for relationships with MRI biomarkers. 47patients with clinically confirmed WE were included (Jan '99-Apr '23; mean age, 53yrs; 70% males). Interrater reliability for imaging findings was substantial (κ = 0.71), with lowest agreements for T2WI (κ = 0.85) compared to all other sequences and for PAG (κ = 0.65) compared to all other typical regions. In consensus, 77% (n = 36/47) of WE cases were rated MRI positive, with FLAIR (n = 36/47, 77%) showing the strongest relation (χ2 = 47.0; P < 0.001) compared to all other sequences. Microbleeds in the MB were detected in four out of ten patients who received SWI, not visible on corresponding T2*WI. Atypical findings were observed in 23% (n = 11/47) of cases, always alongside typical findings, in both alcoholics (n = 9/44, 21%) and non-alcoholics (n = 2/3, 67%). Isolated involvement of structures, explicitly PAG (n = 4/36; 11%) or MB (n = 1/36; 3%), was present but observed less frequently than combined lesions (n = 31/36; 86%). Acut-off width of 2.5 mm for the PAG on 2D axial FLAIR was established between cases and age- and sex-matched controls. An independent association was demonstrated only between short-term memory loss and changes in the MB (OR = 2.2 [95% CI: 1.1-4.5]; P = 0.024). In retrospect, EFNS criteria were positive (≥ 2out of4) in every case, but its count (range, 2-4) showed no significant (P = 0.427) relationship with signal changes on standard MRI. The proposed sequence protocol (FLAIR, DWI, SWI and T1WI + CE) yielded good detection rates for neuroradiological findings in WE, with SWI showing microbleeds in the MB with superior detectability. However, false negative results in about aquarter of cases underline the importance of neurological alertness for the diagnosis. Awareness of atypical MRI findings should be raised, not only in non-alcoholics. There is limited correlation between clinical signs and standard MRI biomarkers.

Non-occlusive Mesenteric Ischemia – A Rare but Deadly Condition

Non-occlusive mesenteric ischemia is a rare but often fatal condition that occurs due to spasms in the splanchnic arteries leading to hypoperfusion, cellular death, bowel ischemia, and eventually perforation. Having a high clinical suspicion in the correct setting is crucial to identify and treating the medical condition quickly. This is a unique case of an 82-year-old Caucasian male who presented with peritonitis secondary to acute mesenteric ischemia caused by hypotension leading to the eventual finding of bowel ischemia and perforation. J MEDICINE 2024; 25: 176-178

Mucinous cystic neoplasm of the liver: A rare case report

Mucinous cystic neoplasm of the liver is a rare cystic neoplasm accounting for approx. 5% of cystic liver in the liver parenchyma. We describe the histomorphology and immunophenotyping features of MCN-L in a 52-year-old woman who came to the surgical department with complaints of pain abdomen for 1.5 months. The ultrasonography showed a septated cyst located centrally in the liver. The CT abdomen showed a large hypodense multiloculated cystic lesion in the liver with thin enhancing septae and multiple small cysts involving the entire left lobe with extension into the right lobe and having a large infra-hepatic exophytic component. A provisional diagnosis of a Hydatid cyst was made. Drainage of the cyst with laparoscopic deroofing was done. Histopathology examination showed a cyst lined by cuboidal to columnar epithelium with mucinous cytoplasm and basally oriented nuclei. Subepithelium shows ovarian-like stroma. MCN-L has a lower frequency as compared to the counterpart of MCN in the pancreas, and further molecular studies are necessary to clarify the biology of MCN-L. The relevance of this rare entity's clinical and radiological suspicion, histological recognition and immunohistochemistry is emphasised.

Dermatomyositis in a young patient: A rare paraneoplastic syndrome of renal cell carcinoma

IntroductionParaneoplastic syndromes are frequent in patients with renal cell carcinoma. Dermatomyositis is an idiopathic inflammatory myopathy that may be associated with neoplasms. This case aims to describe the rare association of dermatomyositis with renal cell carcinoma and to increase clinical suspicion of this neoplasm when systemic rheumatologic symptoms are present.Case presentationA 35‐year‐old female developed severe rheumatologic symptoms (progressive muscle weakness, heliotrope rash, and Gottron's papules). Clinical and laboratory findings indicated dermatomyositis. During the investigation, computed tomography revealed a left kidney solid mass. She underwent a left radical nephrectomy, and histology confirmed renal cell carcinoma. After 3 months, dermatomyositis manifestations disappeared and the patient withdrawn steroid therapy.ConclusionMost paraneoplastic syndromes associated with renal cell carcinoma are only cured with nephrectomy. We highlight the potential role of surgery in dermatomyositis caused by renal cell carcinoma. The recurrence of symptoms related to the syndrome should alert for disease progression.

An international survey of recalcitrant and recurrent tinea of the glabrous skin-A potential indicator of antifungal resistance.

There has been a global rise in cases of dermatophytosis and, in particular, recalcitrant and recurrent cases on tinea of the glabrous skin. This phenomenon, particularly prevalent in India, has been linked to the concerning rise of antifungal resistance. The challenge is amplified by a dearth of comprehensive, international data to understand the global scope and characteristics of such cases. This study aims to collate international insights, focusing on areas outside Europe (as this was previously published), to map the extent and characteristics of clinical and, where possible, laboratory confirmed tinea of the glabrous skin through an online survey administered to dermatologists globally. An online survey was distributed from February 2022 to July 2023 and captured data on respondents' experience of recalcitrant and recurrent tinea of the glabrous skin over the preceding 3 years. A total of 260 responses were received spreads across 36 countries, excluding Europe. In total, 91.7% reported seeing cases of recalcitrant or recurrent tinea of the glabrous skin over the preceding 3 years. Common anatomical sites affected were the trunk and groin. T. mentagrophytes and T. rubrum were the predominant species implicated, and there were low rates of laboratory confirmed dermatophyte resistance. The high rates of reported recalcitrant and recurrent tinea of the glabrous skin underscore an urgent need for global collaborative efforts and enhanced diagnostic measures. The findings advocate for the establishment of a standardized global disease registry, regulation of over-the-counter antifungal and steroid combinations, correlation of clinical suspicion with laboratory confirmed drug resistance and exploration of alternative therapeutic strategies to mitigate the burgeoning challenge of dermatophyte resistance.

Detection of cell-free tumor DNA in cerebrospinal fluid as a diagnostic biomarker for leptomeningeal melanoma metastasis: A case series.

Leptomeningeal melanoma metastases (LMM) are associated with poor survival. Diagnosis is based on clinical presentation, brain MRI and cerebrospinal fluid (CSF) analysis. Inconclusive findings at initial presentation can delay treatment. In this single-center case series, detection of BRAFV600- and NRASQ61-mutant cell-free tumor DNA (cfDNA) in CSF was evaluated as a complementary diagnostic biomarker. In 12 patients with clinical suspicion of LMM, a retrospective analysis of MRI, CSF cytology and cfDNA analysis on 1 mL of CSF using the Idylla® platform was carried out. Nine patients displayed MRI abnormalities suggesting LMM. CSF analysis identified malignant cells in three patients (including one without MRI abnormalities). BRAFV600- or NRASQ61-mutant cfDNA was detected in CSF of nine patients (eight with and one without MRI abnormalities; all patients with positive CSF cytology). Subsequent follow-up confirmed LMM in all patients with positive and in one patient with a negative CSF cfDNA analysis (sensitivity 81.8%; specificity 100%). Our findings suggest that analyzing BRAFV600- and NRASQ61-mutant cfDNA in CSF using the Idylla® platform holds promise as a sensitive and specific complementary diagnostic biomarker for LMM, particularly in case of inconsistency between imaging and CSF cytology. The 110-min analysis can facilitate urgent treatment decisions.

A cross-sectional survey assessing clinicians' perspectives towards redesigning the surveillance model for head and neck cancer: can we do better?

Service delivery of post-treatment surveillance in head and neck cancer (HNC) varies across institutions in Australia. To better understand current practices and develop protocols that maximize service capacity or incorporate emerging technologies, especially in under-resourced regional and remote communities, it is important to obtain the perspectives of clinicians that regularly manage patients with HNC. This cross-sectional study utilized an online survey distributed via email to specialists recruited from HNC-associated networks across Australia. The survey captured information on current practices and explored clinician perspectives towards re-designing the current surveillance model to incorporate telehealth or patient-reported outcome measures (PROMs). Quantitative data was analyzed using descriptive statistics while open-ended survey comments were analyzed using a content analysis approach. Forty participants completed the survey (25 surgeons, 9 medical oncologists, 5 radiation oncologists and 1 oral medicine specialist). Most clinicians used either institution-specific guidelines (44%) or National Comprehensive Cancer Network guidelines (39%), with the remaining 17% using surveillance intervals based on patient symptoms. Following treatment, 53% of participants imaged patients only when there was clinical suspicion of recurrence or new symptoms. Planned surveillance imaging was conducted at 6 or 12-monthly intervals based on the HNC subtype. Fifty-seven percent of clinicians were open to redesigning the surveillance model, specifically in low-risk patients who did not require nasoendoscopic examination. Seventy-one percent had concerns regarding the feasibility of telehealth appointments, citing disparities in digital health equity. Additionally, 61% felt PROMs are currently underutilized and were open to incorporating HNC-specific PROMS into surveillance. Open-ended responses indicated that within the current surveillance model, "fragmented service provision" and "administration issues" were significantly impacting on timing of care. Surveyed HNC clinicians feel that current post-treatment surveillance can be fragmented and potentially lead to delayed care. They are open to incorporating PROMS to assist in surveillance scheduling, especially in low-risk patients.

A cross-sectional survey assessing clinicians' perspectives towards redesigning the surveillance model for head and neck cancer: can we do better?

Service delivery of post-treatment surveillance in head and neck cancer (HNC) varies across institutions in Australia. To better understand current practices and develop protocols that maximize service capacity or incorporate emerging technologies, especially in under-resourced regional and remote communities, it is important to obtain the perspectives of clinicians that regularly manage patients with HNC. This cross-sectional study utilized an online survey distributed via email to specialists recruited from HNC-associated networks across Australia. The survey captured information on current practices and explored clinician perspectives towards re-designing the current surveillance model to incorporate telehealth or patient-reported outcome measures (PROMs). Quantitative data was analyzed using descriptive statistics while open-ended survey comments were analyzed using a content analysis approach. Forty participants completed the survey (25 surgeons, 9 medical oncologists, 5 radiation oncologists and 1 oral medicine specialist). Most clinicians used either institution-specific guidelines (44%) or National Comprehensive Cancer Network guidelines (39%), with the remaining 17% using surveillance intervals based on patient symptoms. Following treatment, 53% of participants imaged patients only when there was clinical suspicion of recurrence or new symptoms. Planned surveillance imaging was conducted at 6 or 12-monthly intervals based on the HNC subtype. Fifty-seven percent of clinicians were open to redesigning the surveillance model, specifically in low-risk patients who did not require nasoendoscopic examination. Seventy-one percent had concerns regarding the feasibility of telehealth appointments, citing disparities in digital health equity. Additionally, 61% felt PROMs are currently underutilized and were open to incorporating HNC-specific PROMS into surveillance. Open-ended responses indicated that within the current surveillance model, "fragmented service provision" and "administration issues" were significantly impacting on timing of care. Surveyed HNC clinicians feel that current post-treatment surveillance can be fragmented and potentially lead to delayed care. They are open to incorporating PROMS to assist in surveillance scheduling, especially in low-risk patients.

Wernicke encephalopathy in a pediatric patient with cannabinoid hyperemesis: A novel case report

AbstractThis case report details a novel case of Wernicke encephalopathy (WE) in a 16‐year‐old boy with obesity and chronic cannabis use. Despite the absence of alcohol use disorder, this adolescent developed classic symptoms of WE, challenging the conventional diagnostic framework. Clinical suspicion for WE was supported by typical magnetic resonance imaging findings, low thiamine levels and rapid clinical improvement postintravenous thiamine supplementation. This case underscores the need for heightened clinical vigilance for WE in patients who present with neurologic symptoms who endorse history of persistent emesis, regardless of their history of alcohol use. It also supports the preemptive administration of thiamine in those at risk of deficiency.

Necrotizing Laryngitis in Patients with Hematologic Disease: The First Case-Report Due to PDR Acinetobacter baumannii and Literature Review

Immunocompromised patients with hematologic diseases may experience life-threatening infections with rather uncommon manifestations. Laryngitis has been described as a potential infection in such vulnerable patients and may result in major complications, ranging from impending airway obstruction to total laryngeal necrosis. Immediate laryngoscopy is of paramount importance, as it provides quantification of laryngeal edema and evidence of necrosis. Documentation of the causative pathogen is usually feasible through tissue culture. In the literature, 14 cases of necrotizing laryngitis have already been published. Here, we present the case of a 38-year-old male with a recent diagnosis of multiple myeloma, who received the first cycle of therapy a few days before admission. The patient presented with neutropenic fever, diarrhea, and multiple organ dysfunction. His course was complicated with hemophagocytic lymphohistiocytosis and stridor. A diagnosis of necrotizing laryngitis attributed to Acinetobacter baumannii invasion of the larynx was established. This manuscript highlights that the management of patients with hematologic disease and necrotizing laryngitis should be coordinated in highly specialized centers and clinicians should have a high level of clinical suspicion and act promptly.

Wernicke encephalopathy in a pediatric patient with cannabinoid hyperemesis: A novel case report

AbstractThis case report details a novel case of Wernicke encephalopathy (WE) in a 16‐year‐old boy with obesity and chronic cannabis use. Despite the absence of alcohol use disorder, this adolescent developed classic symptoms of WE, challenging the conventional diagnostic framework. Clinical suspicion for WE was supported by typical magnetic resonance imaging findings, low thiamine levels and rapid clinical improvement postintravenous thiamine supplementation. This case underscores the need for heightened clinical vigilance for WE in patients who present with neurologic symptoms who endorse history of persistent emesis, regardless of their history of alcohol use. It also supports the preemptive administration of thiamine in those at risk of deficiency.

Necrotizing Laryngitis in Patients with Hematologic Disease: The First Case-Report Due to PDR Acinetobacter baumannii and Literature Review

Immunocompromised patients with hematologic diseases may experience life-threatening infections with rather uncommon manifestations. Laryngitis has been described as a potential infection in such vulnerable patients and may result in major complications, ranging from impending airway obstruction to total laryngeal necrosis. Immediate laryngoscopy is of paramount importance, as it provides quantification of laryngeal edema and evidence of necrosis. Documentation of the causative pathogen is usually feasible through tissue culture. In the literature, 14 cases of necrotizing laryngitis have already been published. Here, we present the case of a 38-year-old male with a recent diagnosis of multiple myeloma, who received the first cycle of therapy a few days before admission. The patient presented with neutropenic fever, diarrhea, and multiple organ dysfunction. His course was complicated with hemophagocytic lymphohistiocytosis and stridor. A diagnosis of necrotizing laryngitis attributed to Acinetobacter baumannii invasion of the larynx was established. This manuscript highlights that the management of patients with hematologic disease and necrotizing laryngitis should be coordinated in highly specialized centers and clinicians should have a high level of clinical suspicion and act promptly.

Pulmonary lymphangitic carcinomatosis-An experience at autopsy.

Pulmonary lymphangitic carcinomatosis is an uncommon mode of metastases, characterized by diffuse infiltration of the lymphatics malignant cells, and is mainly the subject of case reports or a few case series. The aim of this study is to study the clinicopathological features of this entity at autopsy. This is a retrospective study of data collected over an 11-year period at a tertiary-care hospital. Clinicopathological data of all autopsies with lymphangitic carcinomatosis were analyzed with reference to their demographics, clinical presentation, investigations, sites of primary cancer, and other relevant findings at autopsy. Among 255 cases of malignancies encountered in 7521 autopsies during the study period, 43 patients (16.9%) showed pulmonary metastasis with 22 (13 females and 9 males, mean age of 52.04 years) histologically proven lymphangitic carcinomatosis of the lungs. An antemortem diagnosis was made in only 1 of the 22 cases. The most common sites of carcinoma had been the stomach or the lungs (40.9%) and dyspnea had been the main symptom. The lungs, in addition, showed metastatic deposits and arterial thrombi and/or tumor emboli. The most common nonpulmonary site for metastasis was the liver and lymph nodes. Pulmonary lymphangitic carcinomatosis is often an underdiagnosed clinical entity and the presence of acute progressive respiratory failure in patients with epithelial cancers should raise clinical suspicion. This is one of the largest series to be reported at autopsy.

Cardiac sarcoidosis and neurosarcoidosis - multidisciplinary approach for diagnosis.

The current review aims to highlight the role of multidisciplinary approach in the diagnosis of patients with cardiac and neurosarcoidosis. Multidisciplinary approach integrates the available clinical information, imaging and histopathological results aiming to reach a definite or at least provisional diagnosis and allow appropriate management. Multidisciplinary approach is the reference standard for diagnosis of interstitial lung disease and should be strongly considered in complex clinical conditions such as cardiac sarcoidosis (CS) and neurosarcoidosis. Histopathological confirmation of noncaseating granulomatous inflammation provides a definite diagnosis of sarcoidosis involving any organ. However, a provisional high confidence or even definite clinical diagnosis can be reached using multidisciplinary evaluation of all available evidence. The diagnosis of cardiac sarcoidosis and neurosarcoidosis requires the integration of different expertise based on the current diagnostic criteria sets. Identifying typical or at least compatible patterns on advanced imaging modalities (CMR and Fluro-Deoxy-Glucose Positron Emission Tomography (FDG-PET)) seems key for the diagnosis of CS, while a confident diagnosis of extra-cardiac disease supports an at least provisional diagnosis. Similarly, in neurosarcoidosis integrating compatible MRI appearances and cerebrospinal fluid results in patients with systemic sarcoidosis allows an at least provisional diagnosis. Exclusion of alternative differential diagnoses is crucial and requires high clinical suspicion, imaging review expertise and appropriate tests performance. There have been considerable advances in the diagnostic approach of patients with cardiac and neurosarcoidosis. Multidisciplinary approach for both diagnosis and management is required to reach a confident clinical diagnosis and should be applied when possible.

The Value of Magnetic Resonance Enterography Activity Indices in Evaluation of Crohn’s Disease Clinical Activity

Abstract Background Crohn’s disease is a chronic inflammatory segmental bowel disorder characterized by attacks of remission and exacerbation that can significantly affect the patients’ quality of life. Hence monitoring the disease activity is crucial to achieve longer symptom free intervals which may result either from active inflammation and its complications as deep ulceration, fistulae formation and abscesses or sequelae from longstanding inflammatory process as fibrotic scarring and strictures. Aim of the Work to compare the performance of the currently available scoring systems Maria, Clermont, CDMI and MEGS to the clinical disease activity index and endoscopic indices Patients and Methods the study was conducted at the Diagnostic Radiology Unit; Radiology Department, Ain Shams University Hospitals. Over a period of 9 months. Convenience sample of proven cases of Crohn’s disease based on clinical suspicion, biomarkers, endoscopy and histopathological specimens who were referred for MRE enterography at our institution. Results We studied the relevance of 18 different single MR parameters and 5 indices in conjunction with clinical and endoscopic based scores. Our aim was to identify if any of the MR parameters can be used solely or in combination with others (indices) as predictors of disease activity. In our study, we identified that the presence of ulcers reflected the clinical rather than the endoscopic severity. Other individual MR parameters couldn’t predict either the clinical or endoscopic severity. The MaRIA score showed significant correlation with the clinical but not endoscopic score. The simplified MaRIA score reflected both the endoscopic and clinical severity scores regarding their absolute values and severity grade. Neither Diffusion- MaRIA/Clermont nor the CDMI scores could predict the degree of clinical and endoscopic disease severity. MEGS score was the most reliable score in determining the endoscopic activity despite being a consuming score with relative subjectivity in comparison to the forementioned scores. Conclusion MR indices provide an adjunct tool for evaluation of disease activity and identifying the severe disease evidenced by MaRIA, simplified MaRIA and MEGS scores. However, the use of a single MR parameter doesn’t provide a true reflection of the ongoing disease process, even the presence of ulcers and haustral loss may be associated with chronic disease.

Molecular tumor board: molecularly adjusted therapy upon identification and functional validation of a novel ALK resistance mutation in a case of lung adenocarcinoma.

We report a case of a long-term surviving patient with EML4/ALK translocated non-small cell adenocarcinoma of the lung in UICC8 stage IVA. During recurrence under continuous crizotinib therapy, a hitherto insufficiently characterized missense mutation in the ALK gene (Arg1181His) was identified through targeted sequencing. The aforementioned EML4/ALK translocation could still be detected in this situation. Employing a 3D reconstruction of the ALK tertiary structure, considering its interaction with various ALK inhibitors at the molecular binding site, our analysis indicated the presence of a mutation associated with crizotinib resistance. To validate the biological relevance of this previously unknown mutation, we carried out an in vitro validation approach in cell culture in addition to the molecular diagnostics accompanied by the molecular tumor board. The tumor scenario was mimicked through retroviral transfection. Our comparative in vitro treatment regimen paired with the clinical trajectory of the patient, corroborated our initial clinical and biochemical suspicions. Our approach demonstrates preclinical, in silico, and clinical evidence of a novel crizotinib resistance mutation in ALK as well as sensitivity toward brigatinib and potentially lorlatinib. In future cases, this procedure represents an important contribution to functional diagnostics in the context of molecular tumor boards.