Unclear Clinical Diagnosis Research Articles

Monocyte/High-Density Lipoprotein Ratio Is Associated with Atrial High-Rate Episodes within One Year Detected by Cardiac Implantable Electronic Devices.

To investigate the risk factors for predicting atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs). A total of 140 patients with CIED in our hospital from June 2013 to June 2018 were included and were followed up to observe whether they had AHREs. AHRE are defined as atrial rate ≥ 175 times/minute, lasting > 5 minutes, and reviewed by an experienced electrophysiologist with unclear clinical diagnosis. The patients fasted for 12 hours after implantation, and blood samples were collected for biochemical, lipid, and whole blood count detection. Follow-up was regular after discharge to record follow-up data of each patient and conduct statistical analysis. One hundred and forty patients were implanted with dual-chamber pacemakers, their median age was 70 years old, 44.29% were male, 27 patients had AHRE within one year, and AHRE incidence rate was 19.29%. The microcytic to hypochromic (M/H) ratio was calculated for all AHRE patients and compared with the patients without AHRE; the M/H value of AHRE patients was significantly higher. Throughout the entire follow-up period, a total of 44 patients developed AHRE; when adjusted by multivariate analysis, only M/H ratio ≥ 4.5 vs. < 4.5 had statistical significance, and the adjusted hazard ratio value was 4.313 (1.675-11.105). As an indicator, M/H ratio may play an important role in the occurrence and development of atrial fibrillation and can be used as a predictor of AHRE in patients with CIED.

FRI634 Diagnostic Delay Of Diabetic Amyotrophy Is Associated With Complicated Disease Leading To Mental, Physical, And Financial Debilitation- A Case Report

Abstract Disclosure: A.J. Zaidi: None. W. Staehle: None. Introduction: Delay in diagnosis is a major problem impacting medicine, especially if pathology is not very common, like Diabetic amyotrophy. It typically presents with unilateral proximal muscle weakness and pain affecting thighs, hips and buttocks. It is relatively a rare neurological complication of Diabetes Mellitus and prediabetes, affecting approximately 1 percent of the patients. It is commonly underrecognized leading to long course to diagnosis. Case presentation: A 58 year old female presented to clinic with 5 year history of Lower back and left hip pain, slowly progressive leg weakness, with weight loss 25 pounds. Her past medical history included Type 2 diabetes mellitus with A1C 6.9, controlled by Metformin alone. She had multiple previous presentations to local primary care physicians, with unclear clinical diagnosis. She underwent several tests and imaging, was seen by neurologist, orthopedist and spine physician. Her treatments included pain regimens with N-acetylcysteine, Ibuprofen, gabapentin, tizanidine, lidocaine patch, low dose steroids, physical therapy and chiropractor visits. These provided only partial symptomatic relief. She had no other significant history, She lost her job due to being limited by her pain. Exam revealed discomfort to palpation on lower lumbar, generalized atrophy of left thigh muscles, asymmetric proximal weakness, normal sensation and reflexes. Blood work showed normal ESR, CRP, CPK, ANA, myomarker panel, Vit D levels. CSF evaluation was deferred by the patient. Imaging from previous records included Hip X-ray with mild degenerative disease, Lumbar CT with mild arthropathy on the Left L5- S1. Unremarkable lumbar and Sacral MRI. EMG revealed L4 radiculopathy with denervation of L vastus medialis and tibialis anterior, Irritation in S1 nerve root, without denervation. Based on overall investigations, and lack of evidence of alternative diagnosis, it was determined that the patient had Diabetic Amyotrophy. She refused IVIG, treated with prednisone 5mg PO oral for a month, Duloxetine and gabapentin, with significant improvement in pain and weakness. Patient was also connected with appropriate social services, physical and occupational therapy. Conclusion: Diagnostic delay of diabetic amyotrophy can lead to mental, physical, and financial debilitation. Due to low prevalence and broad differential of proximal muscle wasting, it is a challenging to diagnose and remains the diagnosis of exclusion. EMG studies with polyradiculopathy in proximal leg musculature is suggestive. Physicians should have a high clinical suspicion for diabetic amyotrophy to prevent long clinical course leading to harm to the patient. The emphasis is on creating awareness of the disease, and improving communication among clinicians and with patients, which are relatively minor investments to prevent delayed diagnosis of underrecognized complication. Presentation: Friday, June 16, 2023

Zhenwu Decoction:connotation interpretation based on severe cases and modern pathophysiological mechanisms and application in treatment of heart failure in critical care unit

Zhenwu Decoction is recorded in Treatise on Febrile Diseases by an outstanding physician ZHANG Zhong-jing in the Han dynasty. With effect of warming yang, transforming Qi, and promoting urination, Zhenwu Decoction is mainly used to treat edema due to yang deficiency. The studies of the severe and critical cases and the pathophysiological mechanisms have demonstrated that the record of Zhenwu Decoction in Treatise on Febrile Diseases describes the clinical symptoms and therapeutic regimen of acute heart failure. The syndrome treated by this formula may be related to the misdiagnosis and wrong treatment. Due to the difficult distinguishing between cardiogenic dyspnea and pulmonary dyspnea, high doses of Ephedrae Herba may be misused for inducing sweating, which may finally lead to the acute aggravation of heart failure, electrolyte disorder, and pulmonary infection. The syndrome treated by Zhenwu Decoction can illustrate the lack of experience of ancient physicians in treating acute heart failure. The description of &quot;trembling and shivering&quot; may be the clinical manifestation of heart failure, which is an upgraded version of &quot;trembling and shaking&quot; treated by Linggui Zhugan Decoction.(1)In terms of diseases, Zhenwu Decoction is suitable for the treatment of acute or chronic heart failure, cardiorenal syndrome, and diuretic resistance. The decoction is especially suitable for treating whole heart failure, acute heart failure, heart failure with reduced ejection fraction, and heart failure with the syndrome of sold and dampness. In addition, it can be used to treat both type Ⅱ and type Ⅳ cardiorenal syndrome.(2)In terms of symptoms, Zhenwu Decoction can be used for treating chest tightness, palpitations, lower limb edema, difficult urination or increased urine output, fear of cold, pale fat tongue with teeth marks, white and slippery tongue fur, and deep or slow pulse.(3)In terms of the pharmacological mechanism, Zhenwu Decoction treats heart failure following the principle of promoting urination, expanding blood vessels, and invigorating heart in modern medicine. Aconiti Lateralis Radix Praparata is the sovereign herb in the formula, with the recommended dosage of 30-60 g. However, arrhythmia may be caused by high doses of Aconiti Lateralis Radix Praparata, which should be used with concern. In addition to Zhenwu Decoction, Shenqi Pills, Renshen Decoction, Wuling Powder, and Fangji Huangqi Decoction with the effect of invigorating spleen, replenishing Qi, warming Yang, and promoting urination can be used in the recovery stage. The therapy of reinforcing Yang was the last choice for critical cases due to the lack of medical conditions, unclear clinical diagnosis in history, which should be treated objectively now.

Challenging the Norm: Is Routine Use of Cranial CT in Evaluation of Craniosynostosis Necessary?

Cranial CT is routinely taught to be the gold standard for diagnosis of craniosynostosis and used by craniofacial teams for suspected nonsyndromic single suture craniosynostosis. Given the risks associated with infant CTs, do these scans provide significantly enhanced diagnostic accuracy compared to the physical exam when performed by an experienced clinical provider? A retrospective chart review was performed for children who underwent corrective surgery for nonsyndromic, single-suture craniosynostosis over an 11 year period by a single craniofacial team. Ages at presentation and surgery, preoperative clinical diagnosis and imaging, co-existing radiographic findings, and correlation with the intraoperative diagnosis were analyzed. A total of 138 patients were included in this study. The mean age was 4.2 months at initial craniofacial evaluation, and 8.0 months at time of surgery. Twenty-seven patients received imaging prior to our clinic. Of those, 21 had plain radiography and 6 had CT scans. Of the remaining 111 patients referred without imaging, craniosynostosis was clinically diagnosed in 102 (92%), whereas 9 (8%) had an unclear clinical diagnosis. Of these 9, 1 (1%) was diagnosed clinically at follow-up exam, and the remaining 8 (7%) were diagnosed using radiography (3 CT scans, 5 plain radiographs). In all patients, the preoperative diagnosis was confirmed during intraoperative assessment. Cranial CT was not needed by experienced craniofacial providers in 93% of nonsyndromic, single-suture craniosynostosis. Imaging obtained before craniofacial clinic referral may have been unnecessary. These findings question the classic teaching that preoperative cranial CT is the gold standard for diagnosis in infants with nonsyndromic, single-suture craniosynostosis.

Combining Metagenomic Sequencing With Whole Exome Sequencing to Optimize Clinical Strategies in Neonates With a Suspected Central Nervous System Infection.

ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).MethodsWe prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.ResultsEighty-eight neonatal patients were enrolled, and 101 CSF samples were collected. Fourty-three blood samples were collected for WES. mNGS showed a sample diagnostic yield of 19.8% (20/101) compared to 4.95% (5/101) for the conventional methods. In the empirical treatment group, the detection rate of mNGS was significantly higher than that of conventional methods [27% vs. 6.3%, p=0.002]. Among the 88 patients, 15 patients were etiologically diagnosed by mNGS alone, five patients were etiologically identified by WES alone, and one patient was diagnosed by both mNGS and WES. Twelve of 13 diagnoses based solely on mNGS had a likely clinical effect. Six patients diagnosed by WES also experienced clinical effect.ConclusionsFor patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies.

Video laparoscopic diagnostics and surgical tactics for acute diseases of abdominal organs

The article presents the results of video laparoscopy (VLS) performed in 2008–2019 in 5,599 patients in order to diagnose acute diseases of the abdominal organs requiring emergency surgery, identify competing and concomitant diseases, and determine treatment tactics. 2,442 (43.6 %) of them made up group I, with no doubt; 2,656 (47.4 %) – II group, with presumptive reliability; and 501 (9.0 %) – group III, with an unclear clinical diagnosis of the disease. In 2,326 (95.2 %) patients of group I with VLS, the clinical diagnosis was confirmed, in 100 (4.1 %) other diseases were revealed, and in 16 (0.7 %) the diagnosis was not established. Competing diseases were found in 8 patients and concomitant diseases in 4. In 1,641 (61.8 %) patients of group II, VLS made it possible to clarify and differentiate the clinical diagnosis of diseases, in 929 (35.0 %) – to identify other diseases, and in 86 (3.2 %) the diagnosis was not possible. When performing differential diagnosis, 126 other diseases were identified more than the number of patients. Competing diseases were found in 6 patients and concomitant diseases in 6 patients. 356 (71.0 %) patients of group III with VLS were diagnosed with major diseases, 75 (15.0 %) had other diseases, and 70 (14.0 %) were not diagnosed. In 4 patients, competing diseases were found, and in 1 – concomitant disease. Of the 5,427 (96.9 %) patients with the definitive diagnosis of the disease established with VLS, 3,828 (70.5 %) were found to be able to perform VLS operations, in 10 (0.3 %) of them – simultaneous with competing diseases.

Variation in Use of Electrodiagnostic Testing: Analysis From the Michigan Collaborative Hand Initiative for Quality in Surgery

To evaluate factors that predict the use of electrodiagnostic testing (EDS) for patients undergoing carpal tunnel release (CTR). In this cohort study, we analyzed 553 patients who underwent primary CTR from 8 practices between July 1, 2019 and December 1, 2019 by 32 surgeons in the Michigan Collaborative Hand Initiative for Quality in Surgery (M-CHIQS). The M-CHIQS is a collaborative initiative aimed at improving quality in hand surgery. Demographic and clinical characteristics were collected, including the 6-item carpal tunnel symptoms scale (CTS-6) scores and EDS timing. Multilevel logistic regression was used to assess practice and surgeon variation in EDS use related to clinical diagnostic criteria. Of the 553 patients who underwent CTR during the study period, 461 (83.3%) received preoperative EDS. After controlling for patient clinical and demographic characteristics, CTS-6 scores were not associated with receiving any preoperative EDS (lower probability of CTS: odds ratio [OR], 0.94; 95% confidence interval [95% CI], 0.59-1.51), preconsultation EDS (low probability of CTS: OR, 1.00; 95% CI, 0.73-1.38), or postconsultation EDS (low probability of CTS, OR, 1.10; 95% CI, 0.77-1.60). For use of any EDS, 9.3% of the variation in testing was explained at the practice level and 31.1% of the variation in testing was explained at the surgeon level. Variation in EDS use is explained primarily at the practice and surgeon levels and is not related to patient clinical criteria. We recommend that providers and practices assess their use of preoperative EDS and limit its use to patients with an unclear clinical CTS diagnosis, as stated in current clinical practice guidelines. Likewise, providers should be encouraged to use the CTS-6 before prescribing EDS. Limiting the use of EDS to patients with an unclear clinical diagnosis of CTS will reduce costs and improve patient care by eliminating the discomfort and time associated with this test.

Neurological misdiagnoses of lymphoma.

Lymphoma of the nervous system is rare and usually involves the brain, spinal cord, or peripheral nerves. Hence, it has varied clinical presentations, and correct diagnosis is often challenging. Incorrect diagnosis delays the appropriate treatment and affects prognosis. We report 5 patients with delayed diagnosis of lymphoma involving the central and/or peripheral nervous system, initially evaluated for other neurological diagnoses. We also discuss the challenge of diagnosis and appropriate testing. Retrospective review of 2011-2019 records of patients with confirmed nervous system lymphoma diagnosed in a tertiary care medical center. We present 5 adult patients initially evaluated for inflammatory myelopathy, inflammatory lumbosacral plexopathy, atypical parkinsonism, and demyelinating disease of the CNS. Final diagnosis of the nervous system lymphoma was delayed by 4 to 18 months and was based on tissue biopsy in 4, and on CSF and bone marrow examination in 1 patient. Lymphoma may imitate various central and peripheral nervous system disorders. We suggest several red flags that indicate the need to consider lymphoma, including subacute but progressive symptomatic evolution, painful neurological deficit, unclear clinical diagnosis, and transient steroid responsiveness. Correct diagnosis often requires a combination of diagnostic tests, while pathology testing is crucial for early diagnosis and is strongly recommended in the appropriate clinical setting.

Arteriovenous malformation phenotype resembling congenital hemangioma contains KRAS mutations.

Extracranial arteriovenous malformation (AVM) is most commonly caused by a somatic mutation in MAP2K1. We report two patients with vascular anomalies that had an unclear clinical diagnosis most consistent with either an AVM or congenital hemangioma. Lesions were cutaneous, reddish-purple with telangiectasias, present at birth, and had defined borders. Histopathology indicated AVM and both lesions contained somatic KRAS mutations. A rare AVM phenotype exists that shares clinical features with congenital hemangioma.

The role of skin biopsy in diagnosis and management of calciphylaxis: A retrospective analysis

The role of skin biopsy in diagnosis and management of calciphylaxis: A retrospective analysis

Genetic screening in early-onset dementia patients with unclear phenotype: relevance for clinical diagnosis

In a prospective study of dementia in Flanders (Belgium), we observed a substantial fraction of early-onset dementia patients who did not fulfill the criteria for a specific dementia subtype, leaving the patients without a precise clinical diagnosis. We selected 211 of these patients for genetic testing of causal genes linked to neurodegenerative brain diseases. In this group, the onset or inclusion age was 59.9 ± 8.2years and 27.4% had a positive family history. We used a panel of 16 major genes linked to Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and prion diseases. In addition, we tested for the presence of a pathogenic C9orf72 repeat expansion. We identified 13 rare variants in 15 patients, including a carrier of variants in 2 different genes. Six patients (2.84%), carried a mutation in a Mendelian causal gene, that is, APP, MAPT, SOD1, TBK1, and C9orf72. In the other 7 patients, 7 variants were of uncertain significance, including a frameshift mutation in PSEN2, p.G359Lfs*74, in 2 patients sharing a common haplotype, and in LRRK2, p.L2063fs*. Expression studies showed reduced PSEN2 and a near complete loss of LRRK2, in lymphoblast cells or brain material of these patients. Overall, our study underscores the relevance of genetic testing of known causal genes in early-onset patients with symptomatology of neurodegenerative dementia but an unclear clinical diagnosis. A positive genetic result can help to obtain a precise diagnosis as well as a better understanding of the presence of multiple affected relatives in the family.

Diagnostic Potential of Open Lung Biopsy in Mechanically Ventilated Patients with Diffuse Pulmonary Infiltrates of Unclear Aetiology

Acute respiratory failure with bilateral pulmonary infiltrates is a clinical problem with a wide differential diagnosis. We evaluated whether open lung biopsy offered a diagnosis and therapeutic guidance in cases of unclear diagnosis after non-invasive tests. For this purpose, we reviewed 60 cases of open lung biopsy performed between 2002 and 2009 in patients with acute respiratory failure and bilateral infiltrates at the intensive care unit of Ghent University Hospital. Pathological diagnosis was classified as specific or non-specific and its contribution to therapy and decision-making was evaluated by a panel of three intensive care unit physicians. We found that a specific pathological diagnosis was present in 39 open lung biopsy patients (65%; 95% confidence interval 52 to 76%): idiopathic interstitial pneumonia in 24 patients, malignancy in four patients, pulmonary infectious disease in nine patients, and a combination of specific diagnoses in two patients. Open lung biopsy contributed to patient management in 53 cases (88%) as it led to the initiation, modification or discontinuation of therapeutic drugs in 36, and contributed to the decision to continue or withdraw ventilator support in 17. Complications of open lung biopsy were noted in 14 patients (23%). We conclude that open lung biopsy was a useful diagnostic intervention in of a selected group of patients with acute respiratory failure and bilateral infiltrates of unclear clinical diagnosis, as it offered a specific diagnosis in 65%.

Legal regulations of pathology in Russia

Legislation pertaining to pathology in Russia has remained largely unchanged since the 1980s. Almost all regulations refer to the autopsy and documentation of death. The principle of obligatory autopsy for all patients dying in hospitals has remained unchanged. Permission from relatives (or from the deceased in his lifetime) is not required. On the contrary, if relatives wish to take the body without autopsy, they must apply in written form to the head physician (who, in Russia, is the chief executive officer of a hospital) and explain the reasons for the application. It should be commented that today, in many hospitals, almost all such applications (in the absence of contraindications listed below) are granted without pondering on reasons, and the percentage of postmortem investigations has decreased since the former Soviet era. However, recently, the autopsy percentage appears to be increasing again. In the regulations by the Ministry of Health, the conditions are listed when an autopsy is mandatory for patients dying both in and out of a hospital: the unclear clinical diagnosis or cause of death; possible drug overdose or drug reaction; death in connection with medical treatment; a diagnostic procedure or blood transfusion; infectious diseases or suspicion thereof; a malignancy if not histologically verified; death in connection with an environmental accident; pregnancy and perinatal period. Additionally, in all cases when a forensic investigation is indicated, an autopsy has to be performed. Otherwise, postmortem examinations are not mandatory in outpatient cases. The directives contain detailed regulations concerning filling out a death certificate and other documents. The medical part of a death certificate is analogous to that in other countries and has to be filled out in accordance with the International Classification of Diseases. Relatives of a deceased have a formal right to invite a specialist to participate in the autopsy or to request an independent expert examination. The issue of giving out of documents to the patients (or relatives) is specified positively only for records on clinical tests including biopsy or surgical material. Postmortem diagnoses and autopsy protocols are not mentioned in the laws and regulations, which means that the decision to give out copies of these documents (in addition to the death certificate) or not remains with the hospital administration. Normally, these documents are not given out. A voluminous official edition entitled “Voluntary certification system for pathomorphological examinations and patho-anatomic services in health care” appeared in 2007. Certification is defined as official confirmation of compliance of a service with standards. Certification in medicine is performed “along with accreditation and licensing”. A governmental certifying body is planned to be established for this purpose. The volume contains a collection of rules and regulations, some of which are barely relevant to the practice of pathology. A classification of “services” according to their complexity is presented, compiled for accountancy with medical insurance companies (or private payers). Extensive recommendations are given referring to formulation of postmortem diagnoses and filing out of death certificates. Recommendations and listings of equipment for biopsy laboratories are quite outdated: Automatic devices and modern methods are referred to briefly or not mentioned at all. Extensive recommendations, dedicated to safety measures and waste disposal, are quite irrelevant for the practice of pathology: electrotechnical safety, mercury fumes, Int J Legal Med (2008) 122:535–536 DOI 10.1007/s00414-008-0238-2

Arthroscopic findings in wrists with severe post-traumatic pain despite normal standard radiographs

This study assessed the role of diagnostic arthroscopy following a wrist injury in patients with normal standard radiographs, an unclear clinical diagnosis and persistent severe pain at 4 to 12 weeks. Forty-three patients were included after conservative management had failed to improve their wrist pain so that a stability test could be performed satisfactorily and underwent arthroscopy within 12 weeks. Arthroscopy revealed recent pathology in 41 wrists, of which 17 had significant ligament lesions that might have benefited from acute repair. We conclude that patients with marked persistent post-traumatic symptoms despite conservative management are likely to have sustained ligament injuries despite normal radiographs. We therefore recommend that under these circumstances an arthroscopy is carried out within 4 weeks if the patient and surgeon wish to acutely repair significant ligament injuries.