Unique Clinical Entity Research Articles

The impact of cytotoxic therapy on the risk of progression and death in clonal cytopenia(s) of undetermined significance

Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified CCUS patients by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS. A lower proportion of t-CCUS had hypercellular marrows (17.8% vs. 44.8%, P=0.002) but had higher median bone marrow blast percentages. After a median follow up of 2.2 years, t-CCUS had significantly shorter PFS (1.8 vs. 6.3 years, HR 2.1, P=0.007) and median OS (3.6 years vs. not reached, HR 2.3, P=0.007) compared to CCUS. Univariable and multivariable time-to-event analyses showed that exposure to cytotoxic therapy independently accounted for inferior PFS and OS. Despite the similarities in clinical presentation between CCUS and t-CCUS, we show that exposure to prior cytotoxic therapies was an independent risk-factor for inferior outcomes. This suggests that t-CCUS represents a unique clinical entity that needs more stringent monitoring or earlier intervention strategies.

Abstract WMP67: Pump Brain - A Leading Cause of Cortical Cerebral Microbleeds

Introduction: A major cause of cerebral microbleeds (CMBs) is underrecognized and has been attributed to cerebral amyloid angiopathy (CAA) throughout modern medicine. CMBs are acquired by patients undergoing cardiopulmonary bypass (CPB). CPB is utilized for heart and lung transplants, aorta repairs, valve surgeries, mass resections, and coronary artery bypass grafting (CABG) which alone accounts for 400k patients per year. CABGs can be done off CPB in certain patients. Due to their distribution, these CMBs are attributed to CAA, leading to confounding research and suboptimal patient care, especially in those requiring anticoagulation. Methods: This was a single-center, IRB approved, retrospective cohort study of patients who underwent CPB and had postop MRI between 11/1/11 and 3/1/23. Preop and additional postop MRIs were analyzed if available. Outcomes included number and distribution of CMBs, presence of superficial siderosis, FAZEKAS, and CPB duration. We also analyzed MRIs of patients who had off CPB CABG during the same period. Results: Out of 60 patients who underwent CPB, 60 had predominantly cortical CMBs on postop MRI, with a mean of 50 CMBs, and mean age of 61. The 6 patients who had CABG off CPB had 0 CMBs. Higher CMBs were associated with longer CPB duration and with procedures that are associated with more blood loss (p< 0.05). Despite having CMBs, no CPB patients had superficial siderosis, and they had relatively low FAZEKAS scores. Nineteen of the CPB patients had future MRIs and had no evidence of CMB progression. Conclusion: Cortical CMBs are associated with procedures that use CPB and are not seen in off CPB CABG. The CMBs may be related to utilization of cardiotomy suction that exclusively uses roller pumps. CBP related CMBs are a unique clinical entity that is not associated with the progressive cognitive changes and bleeding risk of CAA. While no significant short-term changes are noted, their mechanism and natural history requires further investigation.

Traumatic Aortic Dissection as a Unique Clinical Entity: A Single-Center Retrospective Study.

This study aimed to compare the clinical characteristics, treatment approaches, and outcomes of the Stanford Type B traumatic aortic dissection (TAD) with non-traumatic aortic dissection (NTAD), and assess better management for TAD. We retrospectively analyzed patients who underwent thoracic endovascular aortic repair for Stanford type B aortic dissection at The First Hospital of China Medical University between 2014 and 2022. The patients were divided into TAD and NTAD groups based on whether they had a history of acute trauma. This study ultimately included 65 patients with TAD and 288 with NTAD. We assessed and compared the baseline characteristics, laboratory indicators, imaging features, surgical procedures, and follow-up results between the groups. The TAD group was younger compared to the NTAD group (50.00 [IQR40.00-59.00] vs. 55.00 [IQR 47.00-61.00] years, p = 0.020). A lower percentage of the TAD group had a history of hypertension (20% vs. 71.18%, p < 0.001). The length of aortic dissection was shorter in the TAD group compared to the NTAD group (30.00 [IQR 22.00-40.00] vs. 344.00 [IQR 237.25-400.00] mm, p < 0.001). All patients with TAD underwent TEVAR following the same strategy as NTAD. The mean preoperative duration was 7.00 (IQR 2.00-14.00) days in the TAD group and 11.00 (IQR 8.00-15.00) days in the NTAD group (p < 0.001). TAD showed fewer complications after TEVAR in mid-to-long-term follow-up. TAD is distinct from NTAD. TAD typically presents with more localized lesions than NTAD, and the patients experience a shorter preoperative duration and a better mid-to-long-term outcome.

Acute pancreatitis and pregnancy: Clinical profile, management and maternal-fetal outcomes

Acute pancreatitis during pregnancy, a rare occurrence primarily noted in the third trimester, has been predominantly linked to gallstone lithiasis. This study delves into the multifaceted landscape of this unique clinical entity, aiming to elucidate its manifestation, clinical presentation, therapeutic strategies, and impact on maternal and fetal well-being. A retrospective investigation encompassing cases from January 2009 to October 2021 scrutinized the clinical trajectories of 31 pregnant or postpartum patients with acute pancreatitis. A comprehensive assessment of their profiles, encompassing demographic data, temporal occurrence, symptomatic manifestations, biochemical markers, and imaging findings, formed the basis of this inquiry. The study revealed a mean patient age of 29 years, with 62% being multiparous. The temporal distribution showcased pancreatitis events occurring in various trimesters, with vomiting and epigastralgia as the predominant symptoms. Serum lipase levels, indicative of pancreatic enzyme perturbation, were notably elevated. A concomitant rise in C-reactive protein levels was observed in a significant proportion of cases. Hepatic cytolysis and renal insufficiency were concomitant factors. Diagnosis was facilitated by a combination of clinical symptoms and imaging findings, thus underlining the importance of clinical vigilance. Gallstone etiology emerged as the foremost causative factor, reinforcing the relevance of gallstone lithiasis in this context. Therapeutic measures centered on symptomatic relief, encompassing fluid resuscitation, pain management, and obstetric monitoring. Maternal and fetal outcomes were characterized by an overall positive trajectory, with a maternal mortality rate of 5.8%. Vaginal deliveries constituted the predominant mode of childbirth, with cesarean sections employed in a minority of cases. This study illuminates the complex interplay between acute pancreatitis and pregnancy, shedding light on diagnostic challenges, therapeutic considerations, and the dynamic maternal-fetal interface. The findings underscore the significance of timely diagnosis and management in optimizing outcomes for both maternal and fetal entities. The pursuit of comprehensive insights into this niche domain remains integral to enhancing our understanding and refining clinical practices for this distinctive clinical scenario.

Perceptions, Definitions, and Therapeutic Interventions for Occasional Constipation: A Rome Working Group Consensus Document

Functional constipation is the most common of the disorders of gut-brain interaction, affecting approximately 12% of the world population. Although classically considered a chronic condition, many individuals experience shorter yet repetitive bouts of constipation representing a different clinical entity. There has been increased interest in this latter disorder, which has recently been classified as occasional constipation. This Rome Foundation working group document reflects the consensus of an international team of specialists who summarized currently available research to provide a working definition of and treatment algorithm for occasional constipation. The recommendations herein are based on current evidence, accounting for gaps in the literature as well as international variance in definitions and health seeking behaviors for constipation. The committee members reviewed the scientific literature, focusing specifically on occasional constipation, with the understanding that as a new entity, a paucity of data would be available. We used Rome IV research and clinical definitions to establish the framework for our definition of occasional constipation. Where possible, treatment recommendations were determined on the basis of the earliest extractable data from functional constipation studies, focusing on positive results within the first 2 weeks of treatment. We used the Delphi method to create consensus with 100% agreement between the authors. An evidence-based review of the literature resulted in the definition of occasional constipation as follows: "individuals who experience the presence of at least 1 functional constipation symptom, in the absence of alarm signs or symptoms, occurring at irregular and infrequent intervals, which is bothersome enough to induce a patient to seek medical management." Medical management whether seeking medical care or self-treatment was left to the individual's discretion, and we did not include time anchors because these thresholds require further investigation. Polyethylene glycol and stimulant laxatives are recommended as first-line interventions, whereas magnesium-containing compounds are suggested in individuals failing to respond to these therapies. There are insufficient data to make recommendations for using fiber or stool softeners. Prescription laxatives should be reserved for individuals with chronic constipation. Occasional constipation is a unique clinical entity characterized by infrequent but recurrent symptoms. Data are limited because consensus definitions have been lacking. Establishing a standardized definition and therapeutic recommendations provides a framework for future studies focusing on epidemiologic and symptoms-based outcomes. Further studies are needed to confirm and refine these recommendations.

A 7-year review of clinical characteristics, predisposing factors and outcomes of post-keratoplasty infectious keratitis: the Nottingham infectious keratitis study.

Post-keratoplasty infectious keratitis (PKIK) is a unique sight-threatening clinical entity which often poses significant therapeutic challenges. This study aimed to examine the clinical presentation, risk factors, management, and clinical outcomes of PKIK. This was a retrospective study of all patients who presented to the Queen's Medical Centre, Nottingham, with PKIK between September 2015 and August 2022 (a 7-year period). Relevant data on types of keratoplasty, clinical presentations, causative microorganisms, management, and outcome were analyzed. Forty-nine PKIK cases, including four cases of interface infectious keratitis, were identified during the study period. The most common graft indications for PKP, DALK and EK were failed grafts (9, 37.5%), keratoconus (6, 54.5%) and Fuchs endothelial corneal dystrophy (FECD; 8, 57.1%), respectively. Staphylococcus spp. were the most commonly identified organisms (15, 50.0%). Bullous keratopathy (18, 36.7%), ocular surface disease (18, 36.7%), and broken/loose sutures (15, 30.6%) were the most common risk factors. Concurrent use of topical steroids was identified in 25 (51.0%) cases. Of 31 functioning grafts at presentation, 12 (38.7%) grafts failed at final follow-up with 15 (48.4%) patients retaining a CDVA of ≥1.0 logMAR. The overall estimated 5-year survival rate post-PKIK was 55.9% (95% CI, 35.9%-75.9%), with DALK having the highest survival rate [63.6% (95% CI, 28.9%-98.3%)], followed by EK [57.1% (95% CI, 20.4%-93.8%)] and PKP [52.7% (95% CI, 25.1%-80.3%)], though no statistical difference was observed (p=0.48). PKIK represents an important cause of IK and graft failure. Bullous keratopathy, OSD and suture-related complications are the commonest risk factors, highlighting the potential benefit of prophylactic topical antibiotics (for unhealthy ocular surface) and early suture removal (where possible) in reducing the risk of PKIK. Graft survival may be higher in lamellar keratoplasty following PKIK but larger studies are required to elucidate this observation.

Clinical outcome and therapeutic impact on neuroendocrine neoplasms of the breast: a national cancer database study.

Neuroendocrine neoplasms (NENs) of the breast are rare and not well-studied. NEN are subcategorized as well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC). The objectives of the current study were to review the clinicopathologic features of NENs, therapeutic efficacy of current systemic therapy and clinical outcomes of NEN of the breast. Between 2004 and 2015, 420 NET, 205 NEC, 146 Adenocarcinoma with NE differentiation (ACNED) and 1,479,520 of invasive carcinoma, not otherwise specified (IC-NOS) of the breast were identified in the National Caner Database. Overall survival was compared among groups using Kaplan-Meier method and Log-rank test. Multivariate analyses were performed to identify prognostic factors. After adjusting for other prognostic factors, both NET and NEC of the breast showed significantly worse OS than IC-NOS (HR (95% CI) = 1.41 (1.17, 1.72), p = 0.005 and HR (95% CI) = 2.11 (1.67, 2.67), p < 0.001, respectively). Both NET and NEC benefited from endocrine therapy if the tumors were hormonal receptor positive (median OS for treated with vs without: 125 vs 57months in NET, not reached vs 29months in NEC). NEC also benefited from chemotherapy (median OS for treated with vs without: 42 vs 34months), but not NET. NEN is a unique pathologic and clinical entity, which has worse clinical outcome compared to IC-NOS of the breast. Current therapeutics used in the treatment of IC-NOS improve, but do not fully mitigate, the poorer prognosis of NEN patients. More effective therapy for patients with this unique tumor type are needed.

Clinical Significance of Right Heart Thrombus With and Without an Associated Pulmonary Embolism

BackgroundRight heart thrombus is a rare but serious form of venous thromboembolic disease that may be associated with pulmonary embolism. The prognosis of patients with right heart thrombus presenting without a concomitant pulmonary embolism remains ill-defined. MethodsWe conducted a multi-center observational cohort study to compare patients presenting with right heart thrombus with and without a concurrent pulmonary embolism. The primary endpoint was 90-day all-cause mortality. Multivariable regression was utilized to assess primary and secondary outcomes. ResultsOf 231 patients with right heart thrombus, 104 (45.0%) had a pulmonary embolism at admission. The median age of the cohort was 59.4 years (interquartile range 44.9-71.3). Pulmonary embolism in the setting of a right heart thrombus was associated with an increased adjusted hazard of 90-day mortality (hazard ratio 3.68; 95% confidence interval [CI], 1.51-8.97). Additionally, these patients had a higher adjusted risk of in-hospital mortality (odds ratio [OR] 2.55; 95% CI, 1.15-5.94) and admission to the intensive care unit (OR 2.45; 95% CI, 1.23-4.94). Thrombus mobility (OR 2.99; 95% CI, 1.35-6.78) and larger thrombus sizes (OR 1.04; 95% CI, 1.00-1.07) were associated with development of concurrent pulmonary embolism. ConclusionsPatients with right heart thrombus and pulmonary embolism had a more severe clinical presentation, required more advanced therapies, and had reduced survival compared with those without a concomitant pulmonary embolism. Important variables associated with development of concomitant pulmonary embolism include thrombus mobility and size. Right heart thrombus in the setting of acute pulmonary embolism represents a unique clinical entity that is associated with worse prognosis compared with right heart thrombus only.

A stepwise diagnostic approach for undiagnosed Anemia in children: A model for low-middle income country

BackgroundReaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic studies, which makes undiagnosed anemia a unique clinical entity in tertiary hematology centers. In this study, we aim at plotting a stepwise diagnostic approach in children with undiagnosed anemia while identifying indications for genetic testing. Patients and methodsA one-year cross-sectional study involved 44 children and adolescents with undiagnosed anemia after undergoing an initial routine panel of investigations. They were classified based on mean corpuscular volume (MCV) into 3 groups: microcytic (n = 19), normocytic (n = 14) and macrocytic (n = 11). An algorithm that included four levels of investigations was devised for each category. ResultsAfter applying a systematic diagnostic approach, 33 patients (75 %) were diagnosed of whom 7 (15 %) had combined diagnoses, while 11 (25 %) patients remained undiagnosed. Based on the first, second, third and fourth levels of investigations, patients were diagnosed, respectively, as follows: of the 11 patients, 7 were microcytic, 3 normocytic and 1 macrocytic; of the 7 patients, 2 were microcytic, 2 normocytic, and 3 macrocytic; of 10 patients, 5 were microcytic, 4 normocytic and 1 macrocytic; finally, of the 16 patients, 8 were microcytic, 6 normocytic and 2 macrocytic. Numbers recorded appear higher than the actual number of the patients because some of them were diagnosed by more than one level of investigation. The diagnoses obtained in the microcytic group showed hemoglobinopathies, iron refractory iron deficiency anemia (IRIDA), membrane defects, sideroblastic anemia, hypo-transferrinemia, a combined diagnosis of sickle cell trait and pyropoikilocytosis. The diagnoses also showed a combined diagnosis of hereditary spherocytosis (HS) and alpha thalassemia minor, and a combined diagnosis of iron deficiency anemia and beta thalassemia minor, while 15 % remained undiagnosed. In the normocytic group, the diagnosis revealed autosomal recessive (AR) HS, vitamin B12 deficiency, pyruvate kinase deficiency (PKD), congenital dyserythropoietic anemia (CDA) type I, Diamond Blackfan anemia and beta thalassemia major. In addition, it showed a combined diagnosis of AR HS and CDA type II, a combined diagnosis of AR HS and PKD, and a combined diagnosis of dehydrated stomatocytosis (DHS) and G6PD carrier, meanwhile 20 % remained undiagnosed. Finally, the macrocytic group was diagnosed by vitamin B12 deficiency, sideroblastic anemia, PKD, a combined diagnosis of PKD and G6PD deficiency carrier, while 45 % remained undiagnosed. ConclusionConducting a stepwise approach with different levels of investigations may help reach the diagnosis of difficult anemia without having to resort to unnecessary investigations. Combined diagnosis is an important cause of undiagnosed anemia, especially in countries with high frequency of consanguinity. The remaining 25 % of the patients continued to be undiagnosed, requiring more sophisticated investigations.

Absence of Oligoclonal Bands in Multiple Sclerosis: A Call for Differential Diagnosis.

Immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) are absent in a small group of multiple sclerosis (MS) patients. According to previous research, OCB-negative MS patients differ genetically but not clinically from OCB-positive MS patients. However, whether OCB-negative MS is a unique immunological and clinical entity remains unclear. The absence of OCB poses a significant challenge in diagnosing MS. (1) Objective: The objective of this study was twofold: (1) to determine the prevalence of OCB-negative MS patients in the Uppsala region, and (2) to assess the frequency of misdiagnosis in this patient group. (2) Methods: We conducted a retrospective study using data from the Swedish MS registry (SMSreg) covering 83% of prevalent MS cases up to 20 June 2020 to identify all MS patients in the Uppsala region. Subsequently, we collected relevant information from the medical records of all OCB-negative MS cases, including age of onset, gender, presenting symptoms, MRI features, phenotype, Expanded Disability Status Scale (EDSS) scores, and disease-modifying therapies (DMTs). (3) Results: Out of 759 MS patients identified, 69 had an OCB-negative MS diagnosis. Upon re-evaluation, 46 patients had a typical history and MRI findings of MS, while 23 had unusual clinical and/or radiologic features. An alternative diagnosis was established for the latter group, confirming the incorrectness of the initial MS diagnosis. The average EDSS score was 2.0 points higher in the MS group than in the non-MS group (p = 0.001). The overall misdiagnosis rate in the cohort was 33%, with 22% of misdiagnosed patients having received DMTs. (4) Conclusions: Our results confirm that the absence of OCB in the CSF should raise suspicion of possible misdiagnosis in MS patients and prompt a diagnostic reassessment.

Good-szindróma: egy ritka, szokatlan immunhiányos állapot

Good syndrome is an infrequent and unique clinical entity of associated thymoma and immunodeficiency, first described almost 70 years ago. It is characterized by increased susceptibility to recurrent invasive bacterial and opportunistic infections as well as autoimmune and malignant diseases with an omnious prognosis. The affected patients are mainly middle-aged persons. The most consistent immunological abnormalities are hypogammaglobulinemia and reduced/absent B cells. More recently it was classified as an acquired combined (T, B) immunodeficiency and labelled as a phenocopy. This complex immunocompromised condition can lead to heterogenous clinical phenotypes, making the diagnosis rather challenging. The thymoma is mainly benign, and an incidental finding. Since the thymus plays a critical role in the development of the immune system, the altered tissue structure and microenvironment in thymoma can both predispose to manifestation of immunodeficiency and autoimmunity. The etiopathogenesis of the disease is still unclear, but it is assumed that epigenetic and acquired genetic factors can be highly responsible for its evolvement. Currently there is no specific therapy for Good syndrome. In addition to thymectomy, control of infections, possibly secondary prevention, and regular immunoglobulin replacement are recommended. Orv Hetil. 2023; 164(22): 859-863.

Extrapelvic endometriosis: the mystery of the "black square" or "quintessential classics"?

Endometriosis is still one of the most mysterious and urgent gynecological diseases. The prevalence of endometriosis is steadily increasing, despite the development of innovative methods of diagnosis and treatment. Endometriosis is the presence of a heterotopic endometrium outside the uterine cavity and most often affects the pelvic organs. However, more and more often, the world medical community actualizes the study of extrapelvic endometriosis as a unique clinical entity with specific pathogenetic patterns, approaches to verification, and therapeutic concepts. The article summarizes and systematizes the current scientific data on pathogenesis, clinical phenotypes, and therapy of extrapelvic endometriosis.

Anti-Lactosylceramide antibody positive combined central peripheral demyelination emerging from long-standing juvenile-onset chronic inflammatory polyradiculoneuropathy; a report of two cases

Anti-Lactosylceramide (LacCer) antibodies are associated with neurological inflammation involving both the peripheral and central nervous system (PNS, CNS respectively), however, the documented number of cases is small. Uncertainty remains whether its positivity can identify a unique clinical entity. Here, we describe two anti-LacCer antibody positive cases, both with long histories (> 30 years) of teenage-diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). CNS lesions including the medulla oblongata were observed for the first time in adulthood. We suggest that this secondary progression of CNS lesions in juvenile-onset CIDP can be one of the characteristic features of anti-LacCer antibody associated neurological disorder.

Paclitaxel—A Valuable Tool for Inducing Visceral Pain in Preclinical Testing?

Visceral pain is a unique clinical entity that lacks an effective and safe treatment. Proper preclinical models are essential for assessing new drugs developed for the treatment of this pathology. Few studies report that paclitaxel, an antineoplastic agent, can be used to induce visceral pain in laboratory animals. Our purpose was to investigate the reproducibility of these studies and to develop an animal method that would allow assessing consistent visceral pain. In this study, we used four doses of paclitaxel (3 mg × kg−1; 5 mg × kg−1; 10 mg × kg−1 and 15 mg × kg−1). Visceral pain was evaluated using a scale of abdominal pain immediately after the administration of a single dose of paclitaxel to rats. Tactile and thermal hypersensitivity were assessed using von Frey filaments and the tail flick test initially, at 24 h and 48 h after administration. Rats experienced visceral pain and mechanical and thermal hypersensitivity 24 h after the administration of paclitaxel. The intensity of the pain was increased in a dose-dependent manner with the highest intensity of effect being observed after the administration of a dose of 15 mg × kg−1. Paclitaxel induces visceral pain. The dosage varies depending on the employed strain of rat. This method allows for assessing the efficacy of analgesics to be useful against visceral pain if the paclitaxel dose is adjusted accordingly to the animal strain.

Review of Cervical Schwannomas: Presentation, Pathogenesis, Management, Complications and Future Directions.

Cervical schwannomas are benign peripheral nerve sheath tumors, relatively uncommon pathologies. The purpose of this review is to summarize and expand on the existing literature on cervical schwannomas, focusing on clinical presentation, pathogenesis, surgical and radiologic management and innovative therapies including ultrasound-guided techniques. Pubmed and SCOPUS databases were searched using combinations of terms including "cervical schwannoma", "surgery", "fusion", "complications", "radiosurgery", and others. The findings regarding these unique clinical entities are presented below.

S3414 Goblet Cell Adenocarcinoma Presenting as Appendicitis

Introduction: Goblet Cell Adenocarcinomas (GCAs) are a very rare subtype of appendiceal tumors, with an estimated incidence of 1 per 2 million people. They are not only rare but also unique in terms of their origin. Whereas most cancers arise from one cell line, goblet cell adenocarcinomas are a hybrid of neuroendocrine cells and epithelial cells. The aim of this abstract is to provide an overview of this unique clinical entity. Case Description/Methods: We present a case of a 62-year-old female with past medical history of hypertension, diabetes mellitus and hyperlipidemia who presented to the ED with a one day history of right lower quadrant abdominal pain that had migrated from the periumbilical area, associated with non-bloody vomiting. On arrival, she was stable and her physical examination was significant for tenderness in the right lower quadrant and a positive Rovsing and obturator sign. Labs were remarkable for leukocytosis with left shift. CT scan of the abdomen was done which revealed an inflamed appendix and subsequently patient was taken for a laparoscopic appendectomy. Pathology of the surgical specimen revealed a well differentiated T1NxMx GCA with negative margins and no lymphovascular or perineural invasion. A decision was made to proceed with a right hemicolectomy for the purpose of staging and treatment. Pathology sent after right hemicolectomy revealed no residual GCA with 21 lymph nodes negative for metastasis and negative surgical margins (Figure). Discussion: First described in 1969, GCAs mostly occur in the 5th and 6th decade of life with equal prevalence in both genders. GCAs most commonly present as acute appendicitis but can also present with abdominal pain associated with abdominal mass and weight loss. They can metastasize to the peritoneum, omentum, abdominal wall, and ovaries. Majority of GCAs are diagnosed incidentally on pathological examination of inflamed appendix after appendectomy. The mainstay of treatment is surgical resection with the addition of adjuvant chemotherapy for node-positive (stage III) disease or higher. Due to the rarity of this condition, there is lack of consensus regarding the extent of surgical resection. For stage I disease appendectomy alone maybe sufficient, but higher stages may require hemicolectomy. Prognosis depends on the grade and stage at diagnosis, with one retrospective analysis reporting 5-year survival rates of 100%, 76%, 22%, and 14% for stages I, II, III, and IV, respectively.Figure 1.: 1 and 2 - CT scan of the abdomen showing distended appendix with appendiceal wall thickening and hyperemia, as well as trace periappendiceal edema. 3 - Histologically conventional Goblet cell adenocarcinoma has a “crypt cell pattern” characterized by small round clusters of goblet cells in acinar configuration, resembling colonic crypts. [Pathology slide from Mod Pathol. 2016;29(10):1243-1253. DOI: 10.1038/modpathol.2016.105]).

Clinical Characteristics, Outcomes, and Epidemiological Trends of Patients Admitted With Type 2 Myocardial Infarction

BackgroundType 2 myocardial infarction (T2MI) was first established as a unique entity in 2007. However, its clinical features are not well characterized. This study aimed to determine the clinical characteristics, predictors of mortality, and hospitalization trends of patients with T2MI.MethodsThe National Inpatient Sample database was queried for patients hospitalized in the United States with T2MI (January 2018 to December 2019). Data were used to assess baseline characteristics, primary diagnoses, predictors of mortality, and hospitalization and mortality trends of T2MI.ResultsDuring the 24-month study period, 1,789,485 (76%) patients were admitted with type 1 myocardial infarction (T1MI) and 563,695 (24%) were admitted with T2MI. Patients with T2MI were more likely to be older (71 vs 68 years; P < .001) and female (47.5% vs 38.3%; P < .001), with fewer comorbidities related to coronary atherosclerosis. African Americans were the only race with a significantly higher rate of hospitalization for T2MI (15.9% vs 11.6%; P < .001). The predictors of mortality were similar in both the T2MI and T1MI cohorts. Sepsis (23.47%), hypertensive heart disease (15.35%), and atrial arrhythmias (4.49%) were the most common principal diagnoses for T2MI. T2MI hospitalizations trended consistently upward during the study period. Monthly in-hospital mortality rates were consistently higher for T2MI versus T1MI (P < .001).ConclusionsT2MI is a unique and heterogeneous clinical entity. Despite increased awareness, there is a lack of standardization of medical management and timing for revascularization, even as mortality rates remain persistently elevated compared with T1MI. Certain demographics, including African Americans, may be disproportionately affected.

Tumor Antigenicity and a Pre-Existing Adaptive Immune Response in Advanced BRAF Mutant Colorectal Cancers.

Simple SummaryBRAF mutant metastatic CRCs (BRAF-mCRCs) are considered a unique clinical entity characterized by a dismal prognosis and that do not respond efficiently to both standard chemotherapy and to orally selective inhibitors of BRAFV600E. In this study, the gene expression profiles of 89 immunotherapy-naïve BRAF-CRCs were generated using the PanCancer IO 360 gene expression panel to improve the knowledge of the mechanisms involved in tumor-suppressive immune functions in BRAF-mCRCs. A significant fraction of BRAF-mCRCs shows a hot/inflamed profile and may be potential candidates for responding to immunotherapy. Only a partial overlap between these hot signatures and the presence of microsatellite instability (MSI) was observed, demonstrating that MSI tumors showed a not differential expression of MHC Class I antigen presentation pathway compared with microsatellite-stable tumors. The analysis of gene expression profiles is a promising strategy both for immune profiling of primary tumors before any treatment and for following the evolution of metastatic disease during therapy.The main hypothesis of this study is that gene expression profiles (GEPs) integrating both tumor antigenicity and a pre-existing adaptive immune response can be used to generate distinct immune-related signatures of BRAF mutant colorectal cancers (BRAF-CRCs) to identify actionable biomarkers predicting response to immunotherapy. GEPs of 89 immunotherapy-naïve BRAF-CRCs were generated using the Pan-Cancer IO 360 gene expression panel and the NanoString nCounter platform and were correlated with microsatellite instability (MSI) status and with CD8+ tumor-infiltrating lymphocyte (TIL) content. Hot/inflamed profiles were found in 52% of all cases, and high scores of Tumor Inflammation Signature were observed in 42% of the metastatic BRAF-CRCs. A subset of MSI tumors showed a cold profile. Antigen Processing Machinery (APM) signature was not differentially expressed in MSI tumors compared with MSS cases. By contrast, the APM signature was significantly upregulated in CD8+ BRAF-CRCs versus CD8− tumors. Our study demonstrates that a significant fraction of BRAF-CRCs may be a candidate for immunotherapy and that the simultaneous analysis of MSI status and CD8+ TIL content increases accuracy in identifying patients who can potentially benefit from immune checkpoint inhibitors. GEPs may be very useful in expanding the spectrum of patients with BRAF-CRCs who can benefit from immune checkpoint blockade.

Pediatric Antinuclear Antibody Negative Full-House Nephropathy: A Clinical Conundrum

Introduction: Lupus nephritis is common in pediatric systemic lupus erythematosus (SLE). The presence of full-house immunoglobulin deposits is a unique feature for histopathological diagnosis in lupus nephritis. Our case report highlights two cases with antinuclear antibody (ANA) negative full-house nephropathy (FHN), their clinical phenotypes and intermediate long-term renal outcome. A review of the pediatric literature on this clinical entity ensued. Case Presentation: Two girls, aged three and nine years old presented with acute onset of kidney impairment. One needed temporary dialysis support. Both showed hypocomplementemia and biopsies concurred with FHN. Notably, ANA was absent in both patients. They achieved complete remission soon after introducing immunosuppressive therapy and the disease remained quiescent for many years thereafter. ANA remained negative during surveillance. Conclusions: There have been reports on a possible incomplete form when the characteristic of FHN is seen in isolation. Although natural history of this entity remains uncertain, most literature reports apparent long-term remission following the initial episode. ANA positivity, as an obligatory criterion of diagnosing lupus nephritis (LN), recommended in the new EULAR/ACR 2019 guideline, may raise many uncertainties for this group of patients. There is a need to elucidate whether this should continue to be perceived as part of a lupus continuum or it may be considered a unique clinical entity? Such uncertainties possibly subject the child and his/her caregivers to perpetual mental stress.

Vitamin K antagonist versus novel oral anticoagulants for management of cervical artery dissection: Interactive systematic review and meta-analysis.

Cervical artery dissection (CAD) represents a unique clinical entity with a high risk of ischemic stroke. Vitamin K antagonists (VKA) showed good efficacy in CAD management but are cumbersome to use with potentially higher bleeding rates. Novel oral anticoagulants (NOAC) are easier to use and may have similar effects but lower hemorrhagic risk. In this systematic review, we compare the efficacy of NOAC to VKA as a potential alternative treatment. The literature was searched on Pubmed, PMC, and Embase via API through the Nested Knowledge AutoLit software in February 2022 for studies evaluating both NOAC and VKA. Baseline characteristics, clinical and radiographic outcomes, and hemorrhagic and ischemic complications were collected for single and double-arm studies and analyzed using random-effect subgroup meta-analysis. Overall, 11 studies were included with 699 patients treated with VKA and 53 treated with NOAC (from three studies; two were head-to-head comparative studies). There was no statistical difference in the baseline characteristics of VKA and NOAC patients. The rates of TIA/stroke in VKA and NOAC groups were 12.3% (95% CI; 0%, 28.6%) and 5.7% (95% CI; 0%, 12.2%), respectively. Major bleeding or intracranial bleeding were comparable between groups. Lesions treated with VKA showed angiographic recanalization with a rate of 51.4% (95% CI; 35.6%, 67.1%) and for those treated with NOAC was 58.4% (95% CI; 23.9%, 93.9%). The rates of good clinical outcomes were 79.9% (95% CI; 67.6%, 92.2%) in the VKA group and 91.4% (95% CI; 78.1%, 100%) in NOAC. No statistical difference was noted among any of the outcomes between the two treatment groups. We highlighted comparable efficacy and safety of NOAC to VKA for stroke prevention in CAD. Further head-to-head studies are warranted to validate these results.