Acute Pathologic Findings Research Articles

A Case of Forgotten Poisoning in a Patient Presenting with Speech Disorder

Anticholinergic poisoning is one of the most common causes of poisoning in the emergency department. Beautiful hawthorn (atropa belladonna), which is found in our country, is one of the plants that can cause anticholinergic syndrome. It is important in the differential diagnosis in cases progressing with general status disorder and loss of consciousness and psychotic findings. The onset of anticholinergic intoxication varies depending on the toxin and occurs within one to two hours following oral ingestion. The diagnosis of anticholinergic poisoning is based on clinical findings. Anticholinergic poisoning is easily diagnosed when a history of exposure to an anticholinergic substance is obtained and the patient shows altered mental status, delirium or hallucinations. However, in cases with no history and unknown exposure, the diagnosis of anticholinergic intoxication is considered when clinical signs and symptoms caused by mental status disorder and anticholinergic effects are detected on physical examination. A 75-year-old woman was admitted to the emergency department with complaints of slurred speech, altered consciousness and facial shifting that started about 2 hours ago. On physical examination, the patient was incoopere and disoriented, GCS:12 eyes were spontaneously open, obeying orders but making unintelligible sounds, nuchal rigidity was suspiciously positive, bilateral babinski reflex was positive. On admission vital signs were blood pressure 144/72 mmHg, pulse 98/min, temperature 37 °C, SO2 94%, fingerstick blood glucose 104 mg/dl and ECG was in normal sinus rhythm. There were no acute pathologic findings on both brain CT and brain MR imaging. In the control physical examination, both pupils were mydriatic, IR -/- and the patient had dry mouth. According to the anamnesis obtained from another relative of the patient, it was learned that they ate spinach in the evening and speech disorder started afterwards. The patient was diagnosed with anticholinergic intoxication considering that the spinach eaten by the patient with clinical findings might have been mixed with the beautiful hawthorn weed. In this case report, we aimed to emphasize the importance of detailing the anamnesis and the necessity of a complete systemic examination in patients presenting with confusion and speech disorder.

Universal Chelator-Free Radiolabeling of Organic and Inorganic-Based Nanocarriers with Diagnostic and Therapeutic Isotopes for Internal Radiotherapy

Biomedical application of various nanoparticles (NPs) for bioimaging and therapeutic purposes attracts huge interest. In particular, NPs can be used as nanocarriers of radionuclides for radiotherapy of malignant neoplasms. However, most approaches for NP radiolabeling are complicated, and their transfer into clinical practice is difficult due to their multistep process, limited reproducibility, and lack of an automated radiolabeling procedure. Here, we develop a universal method suitable for radiolabeling of various NPs (either organic or inorganic) for internal radiotherapy of B16-F10 melanoma tumors. The obtained NPs (polylactide, silica, gold, and iron oxide) were labeled with diagnostic (99mTc) and therapeutic (188Re) radionuclides with a high radiolabeling efficiency (∼94–98%) and radiochemical stability (>95%). After their intratumoral administration, these various 188Re-labeled NPs mostly remained in the tumor, inhibiting the tumor growth rate compared to the untreated tumors. The absence of any significant leakage of the radiolabeled NPs in healthy tissues (the liver, heart, kidneys, lungs, and spleen) was confirmed by single-photon emission computed tomography (SPECT) and direct radiometry analysis. Histological analysis revealed no abnormal changes in healthy organs after the therapy (e.g., no acute pathologic findings were detected in the liver and kidneys). As a result, the treatment of mice with 188Re-labeled NPs led to a prolonged survival compared to the control group. Thus, our study provides general guidance for the use of different types of radiolabeled NPs in radionuclide therapy.

Calcium Carbonate Core-Shell Particles for Incorporation of 225Ac and Their Application in Local α-Radionuclide Therapy.

Actinium-225 (225Ac) radiolabeled submicrometric core-shell particles (SPs) made of calcium carbonate (CaCO3) coated with biocompatible polymers [tannic acid-human serum albumin (TA/HSA)] have been developed to improve the efficiency of local α-radionuclide therapy in melanoma models (B16-F10 tumor-bearing mice). The developed 225Ac-SPs possess radiochemical stability and demonstrate effective retention of 225Ac and its daughter isotopes. The SPs have been additionally labeled with zirconium-89 (89Zr) to perform the biodistribution studies using positron emission tomography-computerized tomography (PET/CT) imaging for 14 days after intratumoral injection. According to the PET/CT analysis, a significant accumulation of 89Zr-SPs in the tumor area is revealed for the whole investigation period, which correlates with the direct radiometry analysis after intratumoral administration of 225Ac-SPs. The histological analysis has revealed no abnormal changes in healthy tissue organs after treatment with 225Ac-SPs (e.g., no acute pathologic findings are detected in the liver and kidneys). At the same time, the inhibition of tumor growth has been observed as compared with control samples [nonradiolabeled SPs and phosphate-buffered saline (PBS)]. The treatment of mice with 225Ac-SPs has resulted in prolonged survival compared to the control samples. Thus, our study validates the application of 225Ac-doped core-shell submicron CaCO3 particles for local α-radionuclide therapy.

Myocardial infarction with non-obstructive coronary artery disease. Diagnostic value of intravascular imaging and cardiac resonance

Myocardial infarction with non-obstructive coronary artery disease (MINOCA) is common. Cardiac magnetic resonance (CMR) and intravascular imaging (IVI) may be useful for establishing its etiology. To describe a population with MINOCA and its multi-image assessment using IVI or CMR. Review of medical records, imaging and functional studies of patients with MINOCA treated in three different clinical centers between 2015 and 2019. Twenty-eight patients with MINOCA and IVI were included. Seventy eight percent were women, 46% had hypertension, 32% smoked and 32% had dyslipidemia. At wall motion assessment, 46% presented apical ballooning pattern. In 36% of patients IVI identified lesions that explained the cause of MINOCA, namely plaque disruption (PD) in 18%, spontaneous coronary dissection in 11% and a thrombus without PD in 7%. Forty-six percent of patients had uncomplicated atherosclerotic plaques, and 36% had no pathological findings. CMR was performed in 50% of patients, identifying in all a diagnostic pattern. In nine cases it was compatible with stress cardiomyopathy, three cases had a myocarditis and two cases had transmural infarctions. PD and transmural late gadolinium enhancement were observed in 23% of patients with apical ballooning. Patients with a pattern of myocarditis did not have acute pathological findings at IVI. After a mean follow-up of 16.4±11.4 months, 3 patients with PD died. Among patients with MINOCA, there was a predominance of female gender with low cardiovascular risk factor load. The multi-image assessment allowed greater precision for etiological diagnosis of MINOCA. Apical ballooning was not pathognomonic for stress cardiomyopathy. PD was associated with mortality.

Targeted melanoma radiotherapy using ultrasmall 177Lu-labeled α-melanocyte stimulating hormone-functionalized core-shell silica nanoparticles

Lutetium-177 (177Lu) radiolabeled ultrasmall (~6 nm dia.) fluorescent core-shell silica nanoparticles (Cornell prime dots or C′ dots) were developed for improving efficacy of targeted radiotherapy in melanoma models. PEGylated C′ dots were surface engineered to display 10–15 alpha melanocyte stimulating hormone (αMSH) cyclic peptide analogs for targeting the melanocortin-1 receptor (MC1-R) over-expressed on melanoma tumor cells. The 177Lu-DOTA-αMSH-PEG-C′ dot product was radiochemically stable, biologically active, and exhibited high affinity cellular binding properties and internalization. Selective tumor uptake and favorable biodistribution properties were also demonstrated, in addition to bulk renal clearance, in syngeneic B16F10 and human M21 xenografted models. Prolonged survival was observed in the treated cohorts relative to controls. Dosimetric analysis showed no excessively high absorbed dose among normal organs. Correlative histopathology of ex vivo treated tumor specimens revealed expected necrotic changes; no acute pathologic findings were noted in the liver or kidneys. Collectively, these results demonstrated that 177Lu-DOTA-αMSH-PEG-C′ dot targeted melanoma therapy overcame the unfavorable biological properties and dose-limiting toxicities associated with existing mono-molecular treatments. The unique and tunable surface chemistries of this targeted ultrasmall radiotherapeutic, coupled with its favorable pharmacokinetic properties, substantially improved treatment efficacy and demonstrated a clear survival benefit in melanoma models, which supports its further clinical translation.

Beading of the astrocytic processes (clasmatodendrosis) following head trauma is associated with protein degradation pathways

Objectives: To present the incidence of clasmatodendrosis (injured astrocytic processes) and analyse the association between clasmatodendrosis and the ubiquitin proteasome system (UPS) and autophagy lysosome system (autophagy).Methods: The injured cerebral cortices of 36 autopsy cases were analysed by light microscopy by immunohistochemistry using an anti-glial fibrillary acidic protein (GFAP) antibody and UPS marker antibodies (ubiquitin and lysine 48-linked polyubiquitin chains (K48) and autophagy marker (lysine 63-linked polyubiquitin chains (K63), p62/sequestosome 1 and microtubule-associated protein 1 light chain 3 [LC3]). Double-immunofluorescence staining was used to detect the relationships between p62-K48, p62-K63 and GFAP-K48.Results: Clasmatodendrosis that was immunoreactive to GFAP or K48 was detected by 1 hour up to 14 days following head trauma. The survival time of cases with clasmatodendrosis was significantly shorter than that in cases without clasmatodendrosis (p < 0.01). Involvement of contusion or oedema was significantly frequent in cases with clasmatodendrosis (p < 0.01). There was no significant age difference between cases with clasmatodendrosis and cases without clasmatodendrosis (p = 0.18). Double-immunofluorescence staining for p62-K48 and GFAP-K48 demonstrated clasmatodendrosis with overlapping fluorescence signals.Conclusion: Clasmatodendrosis is associated with UPS-mediated, autophagy and relatively acute pathological findings after traumatic intracranial injury.

An Incidental Finding? Pneumatosis Intestinalis after Minor Trauma

BackgroundPneumatosis intestinalis (PI) refers to the identification of air within the wall of the gastrointestinal tract. This finding often marks serious underlying pathology, which can be potentially surgical in nature. However, this process may also occur within a benign context, for example, in patients who are chronically immunosuppressed. The prevalence of benign PI may be greater than previously anticipated, because its discovery is facilitated by the increasingly widespread use of computed tomography (CT) scanning. ObjectivesWe will illustrate how widespread use of CT scanning after trauma leads to incidental findings, some of which are difficult to distinguish from acute pathologic findings. We will also discuss the differential diagnosis for PI and the associated clinical significance. Case ReportA female patient with two autoimmune disorders requiring immunosuppression presented after minor trauma. Her clinical stability and benign examination led us to refrain from ordering a full radiographic evaluation, including an abdominal CT scan. She was safely discharged; however, per CT several days later, the incidental finding was made of PI with free intraperitoneal air. These findings after trauma commonly prompt an exploratory laparotomy. However, given her persistent stability, we attributed this to immunosuppression rather than to recent trauma. ConclusionThe indications for ordering CT scans after minor trauma must be carefully considered, and incidental findings must be interpreted in the context of the overall clinical scenario.

Transcranial Duplex Sonography and CT Angiography in Acute Stroke Patients

Acute occlusion of cervical or intracranial arteries is the most common cause of ischemic stroke (IS). The aims of the current study were to compare the occurrence of acute pathologic findings in intracranial arteries using transcranial color-coded sonography (TCCS) and computed tomographic angiography (CTA) performed within 3 hours of IS onset and to assess the correlation between the vascular findings on admission and the patient's clinical state on admission and 3 months after the IS. Forty-five consecutive patients with an acute IS were included in the prospective study during an 18-month period. All patients underwent CTA and TCCS within the first 3 hours of symptom onset. A high rate of pathologic findings in the intracranial circulation was found (70.9% in CTA and 77.4% in TCCS examinations). The CTA and TCCS findings with respect to the intracranial arteries were consistent in 87.1% of cases (Cohen's kappa, .797). The sensitivity, specificity, and positive and negative predictive values achieved with TCCS in patients with middle cerebral artery main stem occlusion were 92.3%, 94.4%, and 92.3% and 94.4%, respectively. There was no correlation between the patient's clinical status on admission and 3 months after the onset of the IS and the CTA or the TCCS findings (P > .1 in all cases). A substantial agreement was found between TCCS and CTA in the detection of pathologic findings in intracranial vessels in acute stroke patients. Both methods can be used for this purpose.

Out-of-hospital coronary heart disease death: acute pathological lesions

Background — The majority of deaths due to acute coronary heart disease (CHD) occur outside hospital, unexpectedly, within the first few hours following the onset of the terminal event. Data on the incidence and nature of acute pathological findings in the affected hearts as seen in routine autopsies are somewhat controversial. Detailed pathological examination of coronary arteries and myocardium of such decedents was performed to clarify the situation.Methods and results — Full autopsy and detailed macroscopic and microscopic examination of the coronary arteries and myocardium were performed in 170 men, all registered in the Kaunas Acute Myocardial Infarct Register, who died outside hospital of CHD within 6 hours from the onset of symptoms.Out-of-hospital coronary death was in all cases related to acute ischaemic myocardial lesions, either myocardial infarction (MI) in 92.9% of cases or patchy micronecrosis in 7.1%. In the former group, the following stages of acute infarction were found: early MI (hyperacute phase) in 48.8% of cases, definite MI (displaying grossly identifiable coagulative necrosis) in 21.8% and progressing MI (presence of signs of early MI adjacent to a healing infarction) in 22.3%. Signs of new thrombotic coronary events were found in relation to these acute ischaemic myocardial lesions in 88.8% of cases, as occlusive thrombus in 41.2%, non-occlusive, mural thrombus in 37.0% and microthrombi/microemboli in intramyocardial vessels in 10.6%.Conclusions — Out-of-hospital coronary death most commanly was related to the early or definite stages of myocardial infarction. Accurate identification of these acute ischaemic lesions was based on detailed microscopic examination of the entire ventricular myocardium, with consideration being paid to signs of cardiomyocyte involvement and early inflammatory reaction associated with it.Acute pathology of the affected coronary artery usually confirmed that these myocardial infarct lesions were the cause of the sudden out of-hospital CHD-related deaths.

The high prevalence of severe early posttransplant renal allograft pathology in hepatitis C positive recipients.

In the USA approximately 10% of candidates for renal transplantation have serum antibodies to hepatitis C (HCV). To assess the possible impact of HCV infection on early posttransplant events we assessed allograft complications during the first 6 months following renal transplantation in three groups of adult renal allograft recipients: (1) HCV antibody positive recipients (R-HCV) (n=32); (2) HCV negative recipients who received kidneys from HCV antibody positive donors (D-HCV) (n=48); and (3) HCV negative recipients of HCV negative allografts who were transplanted during the same time period as R-HCV (Ctrl) (n=204). Allograft biopsies were done for evaluation of allograft dysfunction during the first 6 months posttransplant in 58% of Ctrl, 42% of D-HCV, and 63% of R-HCV (not significantly different). The prevalence of acute tubulointerstitial rejection was similar among the 3 groups of patients. In contrast, compared with Ctrl, both R-HCV and D-HCV had a significantly higher prevalence of acute transplant glomerulopathy (Ctrl, 6%; R-HCV, 55%, P<.0001; D-HCV 40%, P=.0004). Acute vascular rejection was more common in R-HCV (60%) than in Ctrl (28%) (P=.009) and the prevalence of chronic vascular rejection was also higher in R-HCV (60%) than in Ctrl (31%) (P=.01). Furthermore, chronic vascular rejection was diagnosed earlier in R-HCV (64% of cases within one month posttransplantation) than in Ctrl (19% within one month) (P=.01). Death censored renal allograft losses occurred in 14% of Ctrl, 17% of D-HCV, and 26% of R-HCV (not significant). In conclusion, R-HCV patients have a high prevalence of severe acute pathologic findings in renal allograft biopsies obtained early after transplantation and develop chronic vascular rejection more often and earlier than HCV negative recipients. These studies also confirm the previously reported association of HCV with acute transplant glomerulopathy.