Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas.

BACKGROUND: Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. METHODS: SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112). RESULTS: SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. CONCLUSION: Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.

The Big Three diagnostic errors through reflections of Japanese internists.

OBJECTIVES: To analyze the Big Three diagnostic errors (malignant neoplasms, cardiovascular diseases, and infectious diseases) through internists' self-reflection on their most memorable diagnostic errors. METHODS: This secondary analysis study, based on a web-based cross-sectional survey, recruited participants from January 21 to 31, 2019. The participants were asked to recall the most memorable diagnostic error cases in which they were primarily involved. We gathered data on internists' demographics, time to error recognition, and error location. Factors causing diagnostic errors included environmental conditions, information processing, and cognitive bias. Participants scored the significance of each contributing factor on a Likert scale (0, unimportant; 10, extremely important). RESULTS: The Big Three comprised 54.1 % (n=372) of the 687 cases reviewed. The median physician age was 51.5 years (interquartile range, 42-58 years); 65.6 % of physicians worked in hospital settings. Delayed diagnoses were the most common among malignancies (n=64, 46 %). Diagnostic errors related to malignancy were frequent in general outpatient settings on weekdays and in the mornings and were not identified for several months following the event. Environmental factors often contributed to cardiovascular disease-related errors, which were typically identified within days in emergency departments, during night shifts, and on holidays. Information gathering and interpretation significantly impacted infectious disease diagnoses. CONCLUSIONS: The Big Three accounted for the majority of cases recalled by Japanese internists. The most relevant contributing factors were different for each of the three categories. Addressing these errors may require a unique approach based on the disease associations.

In-Hospital Onset of Transient Myoclonic State in Older Adults: A Case Report.

Background: Transient myoclonic (TM) state in older adults is a neurological condition characterised by short-lived, repetitive myoclonus without consciousness disturbance. First reported in 1992, it predominantly affects older individuals with chronic diseases. Despite its clear symptomatology, TM often remains under-recognised, leading to potential misdiagnoses. Case description: We report a case of a 68-year-old woman with a history of chronic heart failure who developed TM during hospitalisation following medication adjustment for acute heart failure. The patient, who had no history of intracranial disease or epilepsy, experienced acute involuntary movements of the face and limbs three days after diuretic adjustment. She responded well to intravenous diazepam and oral clonazepam, with no recurrence of symptoms post-treatment. Discussion: TM presents with bilateral, irregular, and repetitive myoclonus, mostly affecting the head, neck and upper extremities. Diagnosis is clinical, based on symptomatology and normal laboratory results. This case underscores the importance of recognising TM in differential diagnosis, especially in older patients in the acute or recovery phase of infection, or with medication changes. The potential role of fluid volume changes in TM pathophysiology in patients with underlying conditions such as hypertension or chronic heart failure is also highlighted. This case emphasises the need for heightened awareness and knowledge of TM among healthcare professionals. Conclusions: TM, though rare, requires awareness among clinicians for accurate diagnosis and management. It is crucial to avoid misdiagnosis and unnecessary interventions, and to provide appropriate information during care transitions, particularly in older adults with chronic conditions. LEARNING POINTS: Transient myoclonic (TM) state is a rare neurological condition in older adults, characterised by brief and repetitive myoclonus, primarily affecting the head, neck and upper extremities.The distinctive clinical diagnostic feature is myoclonus occurring without disturbances in consciousness, without amnesia or paralysis, while retaining the ability to perform directed movements. This condition can manifest at rest, may worsen with posture or movement, and tends to improve during sleep.Management strategies include ensuring smooth care transitions, avoiding misdiagnosis and educating patients and families about the risk of recurrence.

Three Subtypes of Cutaneous Nerve Entrapment Syndrome: A Narrative Review.

Anterior, lateral, and posterior cutaneous nerve entrapment syndromes have been proposed as etiologies of trunk pain. However, while these syndromes are analogous, comprehensive reports contrasting the three subtypes are lacking. We therefore reviewed the literature on anterior, lateral, and posterior cutaneous nerve entrapment syndrome. We searched the PubMed and Cochrane Library databases twice for relevant articles published between March and September 2022. In addition to 16 letters, technical reports, and review articles, a further 62, 6, and 3 articles concerning anterior, lateral, and posterior cutaneous nerve entrapment syndromes, respectively, were included. These syndromes are usually diagnosed based solely on unique history and examination findings; however, the diagnostic process may be prolonged, and multiple re-evaluations are required. The most common first-line treatment is trigger point injection; however, the management of refractory cases remains unclear. Awareness of this disease should be expanded to medical departments other than general medicine.

Protecting the primary care physicians' well-being.

Seminar participants collaborated as a team to improve their organization, work environment, and labor issues using the Plan-Do-Check-Act (PDCA) cycle. The PDCA cycle helps healthcare providers identify risks and hazards in their work environment and address daily issues. It guides them in planning and executing improvements while enabling progress tracking and encouraging further considerations for implementation.

Osmotic Demyelination Syndrome in a Patient with Diabetic Ketoacidosis Despite No Rapid Sodium Correction.

Osmotic demyelination syndrome (ODS) occurs in patients with diabetes and hyponatremia. We herein report a case of ODS with chorea detected on serial magnetic resonance imaging (MRI), despite no prompt hyponatremia correction. A 74-year-old man with cirrhosis and uncontrolled type 2 diabetes developed an altered mental status and chorea during treatment for diabetic ketoacidosis (DKA). Despite no rapid sodium correction and normal initial brain MRI findings, serial MRI revealed ODS-related abnormalities. Clinicians should consider ODS in patients with DKA and a hyperosmolar hyperglycemic state displaying unconsciousness and neurological manifestations, including chorea, even without substantial changes in serum sodium levels. An MRI re-examination can help capture missing ODS complications.

Diagnostic errors in uncommon conditions: a systematic review of case reports of diagnostic errors.

OBJECTIVES: To assess the usefulness of case reports as sources for research on diagnostic errors in uncommon diseases and atypical presentations. CONTENT: We reviewed 563 case reports of diagnostic error. The commonality of the final diagnoses was classified based on the description in the articles, Orphanet, or epidemiological data on available references; the typicality of presentation was classified based on the description in the articles and the judgment of the physician researchers. Diagnosis Error Evaluation and Research (DEER), Reliable Diagnosis Challenges (RDC), and Generic Diagnostic Pitfalls (GDP) taxonomies were used to assess the factors contributing to diagnostic errors. SUMMARY AND OUTLOOK: Excluding three cases in that commonality could not be classified, 560 cases were classified into four categories: typical presentations of common diseases (60, 10.7 %), atypical presentations of common diseases (35, 6.2 %), typical presentations of uncommon diseases (276, 49.3 %), and atypical presentations of uncommon diseases (189, 33.8 %). The most important DEER taxonomy was "Failure/delay in considering the diagnosis" among the four categories, whereas the most important RDC and GDP taxonomies varied with the categories. Case reports can be a useful data source for research on the diagnostic errors of uncommon diseases with or without atypical presentations.

Usefulness of magnetic resonance imaging for acute abdominal pain in a pregnant woman: A case of idiopathic renal hemorrhage.

Acute abdominal pain in pregnant women may complicate the diagnostic process of acute abdominal pain because of anatomical and physiological changes and limitations of computed tomography examinations related to radiation exposure. Here, we present the case of a 35-year-old female in her 10th week of pregnancy who was seen in the emergency department with unilateral abdominal pain and gross hematuria. Ultrasound detected only hydronephrosis and failed to identify ureteral stones, but magnetic resonance imaging revealed a diagnosis of idiopathic renal hemorrhage and intraductal ureteral hematoma, not ureteral stones. Although magnetic resonance imaging for pregnant women has the disadvantages of prolonged scan time and difficulty in image interpretation, no harm or complications to the mother or fetus have been reported. Magnetic resonance imaging may be considered in assessing acute abdominal pain in pregnant women, especially when the diagnosis is uncertain, based on shared decision-making with the patient and assessing the clinical situation and availability.

Cervical Angina as a Cause of Non-Cardiac Chest Pain: A Case Report.

Cervical angina is a form of non-cardiac chest pain that originates in the cervical spine or cervical cord; it is an under-recognized and easily underdiagnosed condition. Patients with cervical angina often report delayed diagnosis. Here, we report the case of a 62-year-old woman with a history of cervical spondylosis and undiagnosed recurrent chest pain who presented with numbness in the left upper arm and was diagnosed with cervical angina. Although most cases of cervical angina involve uncommon self-limited diseases that improve with conservative treatment, timely diagnosis can reduce patient anxiety and unnecessary office visits and tests. The critical aspect of chest pain evaluation is to rule out fatal disease. Once fatal disease is ruled out, cervical angina should be considered in differential diagnosis if there is a history of cervical spine disease, if the pain radiates to the arm, if it is elicited by cervical spine range of motion or upper extremity movement, or if the chest pain lasts less than a few seconds.

Rapid-kinetics degron benchmarking reveals off-target activities and mixed agonism-antagonism of MYB inhibitors.

Attenuating aberrant transcriptional circuits holds great promise for the treatment of numerous diseases, including cancer. However, development of transcriptional inhibitors is hampered by the lack of a generally accepted functional cellular readout to characterize their target specificity and on-target activity. We benchmarked the direct gene-regulatory signatures of six agents reported as inhibitors of the oncogenic transcription factor MYB against targeted MYB degradation in a nascent transcriptomics assay. The inhibitors demonstrated partial specificity for MYB target genes but displayed significant off-target activity. Unexpectedly, the inhibitors displayed bimodal on-target effects, acting as mixed agonists-antagonists. Our data uncover unforeseen agonist effects of small molecules originally developed as TF inhibitors and argue that rapid-kinetics benchmarking against degron models should be used for functional characterization of transcriptional modulators.

Five strategies on writing research papers for beginners and young general medicine doctors.

We propose five important strategies for young generalists to write original research and papers. We hope that even beginners will understand and practice these five strategies, and help young generalist to write research papers based on clinical questions that arise in their daily practice.

Leukemia core transcriptional circuitry is a sparsely interconnected hierarchy stabilized by incoherent feed-forward loops.

Lineage-defining transcription factors form densely interconnected circuits in chromatin occupancy assays, but the functional significance of these networks remains underexplored. We reconstructed the functional topology of a leukemia cell transcription network from the direct gene-regulatory programs of eight core transcriptional regulators established in pre-steady state assays coupling targeted protein degradation with nascent transcriptomics. The core regulators displayed narrow, largely non-overlapping direct transcriptional programs, forming a sparsely interconnected functional hierarchy stabilized by incoherent feed-forward loops. BET bromodomain and CDK7 inhibitors disrupted the core regulators' direct programs, acting as mixed agonists/antagonists. The network is predictive of dynamic gene expression behaviors in time-resolved assays and clinically relevant pathway activity in patient populations.

Medical Malpractice and Diagnostic Errors in Japanese Emergency Departments.

INTRODUCTION: Emergency departments (ED) are unpredictable and prone to diagnostic errors. In addition, non-emergency specialists often provide emergency care in Japan due to a lack of certified emergency specialists, making diagnostic errors and associated medical malpractice more likely. While several studies have investigated the medical malpractice related to diagnostic errors in EDs, only a few have focused on the conditions in Japan. This study examines diagnostic error-related medical malpractice lawsuits in Japanese EDs to understand how various factors contribute to diagnostic errors. METHODS: We retrospectively examined data on medical lawsuits from 1961-2017 to identify types of diagnostic errors and initial and final diagnoses from non-trauma and trauma cases. RESULTS: We evaluated 108 cases, of which 74 (68.5%) were diagnostic error cases. Twenty-eight of the diagnostic errors were trauma-related (37.8%). In 86.5% of these diagnostic error cases, the relevant errors were categorized as either missed or diagnosed incorrectly; the others were attributable to diagnostic delay. Cognitive factors (including faulty perception, cognitive biases, and failed heuristics) were associated with 91.7% of errors. Intracranial hemorrhage was the most common final diagnosis of trauma-related errors (42.9%), and the most common initial diagnoses of non-trauma-related errors were upper respiratory tract infection (21.7%), non-bleeding digestive tract disease (15.2%), and primary headache (10.9%). CONCLUSION: In this study, the first to examine medical malpractice errors in Japanese EDs, we found that such claims are often developed from initial diagnoses of common diseases, such as upper respiratory tract infection, non-hemorrhagic gastrointestinal diseases, and headaches.

Evaluation of the usefulness of costovertebral angle tenderness in patients with suspected ureteral stone.

Background: The usefulness of costovertebral angle (CVA) tenderness for the diagnosis of a suspected ureteral stone remains controversial. Methods: This single-center, retrospective, observational study included patients aged 16-64 years with acute-onset unilateral lower back pain or abdominal pain. The diagnostic accuracy of CVA tenderness was investigated. Results: In total, 132 patients met the criteria; 80 were diagnosed with ureteral stones. The sensitivity and specificity of CVA tenderness were 0.65 and 0.50, respectively; positive and negative likelihood ratios were 1.3 and 0.7, respectively. Conclusions: CVA tenderness cannot be used as a single diagnostic indicator to confirm or exclude ureteral stone diagnosis.

Deprescribing antacids after the diagnosis of Clostridioides difficile infection: A single-center observational study.

Overuse of antacids is associated with the development and recurrence of Clostridioides difficile infection (CDI). Discontinuation of unnecessary antacids for CDI management is advocated; however, the clinical pervasiveness on the discontinuation of antacids remains unclear. We conducted a single-center retrospective observational study to determine the rate of antacid discontinuation following CDI diagnosis. Among 51 patients (58 infections; median age 76.5 years, range 69-82; 53.5% women) treated with antimicrobials against C. difficile, 41 had been treated with antacids, and of these, 18 exhibited no indication for antacid administration. However, none had discontinued antacid use. While CDI provides an opportunity for antacid stewardship, it is not implemented in clinical practice. In addition to the efforts of individual clinicians, the dissemination of knowledge of the indications and side effects of antacids, establishment of a multidisciplinary support system, and creation and implementation of a clinical stewardship pathway are necessary to increase the deprescription of antacids in patients with CDI.

Serum amyloid A1 recruits neutrophils to the invasive front of T1 colorectal cancers.

BACKGROUND AND AIM: The tumor microenvironment plays an essential role in the development and progression of colorectal cancer (CRC). We recently reported that crosstalk between CRC cells and tumor-associated macrophages (TAMs) via serum amyloid A1 (SAA1) promotes invasion by T1 CRCs. In the present study, we aimed to clarify the role of neutrophils in early CRCs. METHODS: Immunohistochemical analysis of CD66b, chemokine CXC motif ligand 8 (CXCL8 or interleukin-8, IL-8) and matrix metalloproteinase-9 (MMP-9) was performed using primary T1 CRCs (n = 49). The HL-60 human promyelocytic leukemia cell line and THP-1 human monocytic leukemia cell line were used to obtain neutrophil-like and macrophage-like cells, respectively. Boyden chamber assays were used to analyze cell migration and invasion, and quantitative RT-PCR was used to analyze gene expression. RESULTS: Immunohistochemical analysis revealed accumulation of neutrophils at the SAA1-positive invasive front of T1 CRCs. Experiments using HL-60 cells suggested that treatment with SAA1 induced neutrophil migration and expression of CXCL8 and MMP-9 in neutrophils and that neutrophils promote CRC cell migration and invasion. Immunohistochemistry confirmed accumulation of CXCL8- or MMP-9-positive neutrophils at the SAA1-positive invasive front of T1 CRCs. Moreover, co-culture experiments using CRC, THP-1 and HL-60 cells suggested that CRC cells activated by macrophages upregulate CXCL8 and MMP-9 in neutrophils. CONCLUSIONS: Our results suggest that interplay between macrophages and CRC cells leads to recruitment of neutrophils to the invasive front of T1 CRCs and that SAA1 secreted by CRC cells activate neutrophils to promote invasion.

Two Cases of Acute Urinary Retention Associated With Acute Sarcopenia in Older Women.

Acute urinary retention during hospitalization is a poor prognostic predictor. Therefore, prevention of the same is important. Herein, we describe two cases of acute urinary retention in older women admitted to the hospital for acute illness, with severe sarcopenia being the only predisposing cause. Both women developed urinary problems shortly after admission. In both, acute urinary retention was preceded by an in-hospital period of poor nutritional intake and a lack of progress in rehabilitation. There was no evidence of genitourinary disorder, neurological disease, drug-induced dysuria, bone fracture, or pain. Both patients presented with severe sarcopenia and severe frailty.Although the loss of mass in the voiding muscles is difficult to detect, the possibility of dysuria as one of the complications of acute and severe sarcopenia was indicated in our patients. Of note, however, is that many patients with severe sarcopenia do not develop dysuria. Therefore, accumulating evidence on the possible association between severe sarcopenia and dysuria is needed to inform prevention.