Clinical Characteristics and Local Histopathological Modulators of Endometriosis and Its Progression.

Endometriosis (E) and adenomyosis (A) are associated with a wide spectrum of symptoms and may present various histopathological transformations, such as the presence of hyperplasia, atypia, and malignant transformation occurring under the influence of local inflammatory, vascular and hormonal factors and by the alteration of tumor suppressor proteins and the inhibition of cell apoptosis, with an increased degree of lesion proliferation. MATERIAL AND METHODS: This retrospective study included 243 patients from whom tissue with E/A or normal control uterine tissue was harvested and stained by histochemical and classical immunohistochemical staining. We assessed the symptomatology of the patients, the structure of the ectopic epithelium and the presence of neovascularization, hormone receptors, inflammatory cells and oncoproteins involved in lesion development. Atypical areas were analyzed using multiple immunolabeling techniques. RESULTS: The cytokeratin (CK) CK7+/CK20- expression profile was present in E foci and differentiated them from digestive metastases. The neovascularization marker cluster of differentiation (CD) 34+ was increased, especially in areas with malignant transformation of E or A foci. T:CD3+ lymphocytes, B:CD20+ lymphocytes, CD68+ macrophages and tryptase+ mast cells were abundant, especially in cases associated with malignant transformation, being markers of the proinflammatory microenvironment. In addition, we found a significantly increased cell division index (Ki67+), with transformation and inactivation of tumor suppressor genes p53, B-cell lymphoma 2 (BCL-2) and Phosphatase and tensin homolog (PTEN) in areas with E/A-transformed malignancy. CONCLUSIONS: Proinflammatory/vascular/hormonal changes trigger E/A progression and the onset of cellular atypia and malignant transformation, exacerbating symptoms, especially local pain and vaginal bleeding. These triggers may represent future therapeutic targets.

A 40-Year-Old Man with a 7-Year History of Polyarthritis and a Late Diagnosis of Whipple Disease: A Journey to Resolve the Mystery.

BACKGROUND Whipple disease (WD) is rare, with an incidence of only a few patients per million. It is caused by infection with the gram-positive bacterium Tropheryma whipplei, and presents with symptoms that include joint pain, fever, diarrhea, and weight loss. This report is of a 40-year-old man with a 7-year history of polyarthritis and a late diagnosis of Whipple disease. The atypical nature of his symptoms led to misdirection and misdiagnosis for years. CASE REPORT A middle-aged white man with seronegative migratory polyarticular arthritis underwent 7 years of treatment with steroids, disease-modifying anti-rheumatic drugs (DMARDs), and a TNF (tumor necrosis factor)-alpha inhibitor, all without any clinical improvement. Throughout this period, he had persistent loose stools and iron-deficiency anemia. Extensive diagnostic investigations for various possibilities yielded negative results. However, after 7 years, he began displaying clinical signs of malabsorption. This prompted further evaluation, including an upper-gastrointestinal endoscopy and biopsy, which revealed the presence of PAS (periodic acid-Schiff)-positive Treponema whipplei, which led to the diagnosis of WD. Following initiation of appropriate treatment, the patient experienced complete resolution of symptoms. Retrospectively, all the pieces of this puzzle fell into place, providing a comprehensive understanding of the prolonged medical challenge the patient faced. CONCLUSIONS This case illuminates the diagnostic challenge faced when dealing with migratory polyarticular inflammatory arthritis and fever. This report has highlighted that Whipple disease can be associated with multiple symptoms and signs, which can result in a delay in diagnosis. However, once the diagnosis is confirmed, antibiotic treatment is effective.

Acute encephalomyelitis in a 52-year-old male post messenger ribonucleic acid severe acute respiratory syndrome coronavirus 2 vaccination: a case report.

BACKGROUND: Acute disseminated encephalomyelitis is a well-known, but rare, side effect of some vaccines, or symptom following a febrile illness. CASE: A 69-year-old, otherwise healthy Hispanic male presented with acute fever, confusion, and later progressive weakness after receiving the first dose of the mRNA-1273 (Moderna) severe acute respiratory syndrome coronavirus 2 vaccine. Considering the progressive deterioration of the patient, despite being on multiple immunosuppressive agents, a brain biopsy was obtained, which revealed nonspecific meningoencephalitis. CONCLUSION: In this case, we highlight the need for a regulatory framework to assist clinicians and patients with coverage of treatment for acute disseminated encephalomyelitis. The use of intravenous immunoglobulin in conjunction with glucocorticoids seems to be an effective treatment option.

Rituximab-Induced Colitis and Esophagitis in a Patient With Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis that affects many organ systems with varying disease severity. GPA commonly affects the sinuses and lung parenchyma. However, GPA can affect the gastrointestinal tract and may present as colitis. Immunosuppressive therapy, like rituximab (RTX), is used for the management of this disease. Rituximab is generally well-tolerated but has rare side effects that have been shown to mimic colitis in inflammatory diseases. Our case is a 44-year-old female with a history of GPA who presented with dysphagia, abdominal pain, and diarrhea. The patient received a maintenance dose of RTX six months before the presentation. The patient was seronegative for anti-neutrophilic cytoplasmic antibodies against proteinase 3 (PR3 ANCA). Infectious etiology was ruled out. Esophagogastroduodenoscopy (EGD) and colonoscopy showed esophageal bleeding ulcers and diffuse colonic inflammation, respectively. Pathology was consistent with esophagitis and colitis. Colonic mucosal biopsy failed to show evidence of vasculitis. The patient was treated with sucralfate and intravenous pantoprazole with an improvement in the symptoms. The repeat endoscopy on an outpatient basis showed the patient had full mucosal healing, including histological healing. Our patient likely had rituximab-induced colitis and esophagitis.

Histopathological lesions induced by stroke in the encephalon.

Strokes are conditions with a high degree of morbidity and mortality worldwide. These conditions profoundly affect the quality of life of patients; in addition to physical disabilities, patients present various mental disorders, such as mood disorders, anxiety, depression, behavioral disorders, fatigue, etc. Microscopic lesions of the brain parenchyma explain the clinical symptoms and correlate with the severity of the stroke. Our study consisted of the histopathological (HP) and immunohistochemical analysis of brain fragments, collected from 23 patients, with a clinical and imagistic diagnosis of stroke, who died during hospital admission. The microscopic analysis showed that both neurons and glial cells are affected in the ischemic focus. Neuronal death in the ischemic focus was mostly caused by cell necrosis and only about 10% by apoptosis. Regarding vascular lesions, it was observed that the most frequent HP lesion of intracerebral arterioles was arteriosclerosis. The lumen of the arterioles was reduced, and the vascular endothelium had a discontinuous aspect, which indicates a change in the blood-brain barrier. Sometimes the arteriole lumen was completely obstructed, with fibrinoid necrosis in the internal and middle tunic, or with the proliferation of fibroblasts and the formation of young intraluminal connective tissue. Intraparenchymal blood capillaries in the ischemic area showed endothelium discontinuities, lumen collapse, and sometimes massive perivascular edema. As for neuroinflammation, the presence of numerous neutrophils, lymphocytes, plasma cells and macrophages was found in the ischemic focus, forming a complex and inhomogeneous cellular mixture. Of the inflammatory cells present in the ischemic focus and in the ischemic penumbra area, the most numerous were the macrophages. The HP analysis showed that neuroinflammation is very complex and different in intensity from one patient to another, most likely due to associated comorbidities, age, treatment administered until death, etc.

Uterine Perforation as a Complication of the Intrauterine Procedures Causing Omentum Incarceration: A Review.

OBJECTIVE: Omentum involvement resulting from uterine perforation is a rare complication following intrauterine procedures that might require immediate intervention due to severe ischemic consequences. This review examines the prevalence of this complication, risk factors, the mode and timing of diagnosis, the proper management and the outcome. METHODS: A systematic literature search was conducted on PubMed, PubMed Central and Scopus using uterine perforation, D&C, abortion and omentum as keywords. The exclusion criteria included the presence of the uterus or placenta's malignancy and uterine perforation following delivery or caused by an intrauterine device. RESULTS: The review included 11 articles from 133 screened papers. We identified 12 cases that three evaluators further analysed. We also present the case of a 32-year-old woman diagnosed with uterine perforation and omentum involvement. The patient underwent a hysteroscopic procedure with resectioning the protruding omentum into the uterine cavity, followed by intrauterine device insertion. CONCLUSION: This paper highlights the importance of a comprehensive gynaecological evaluation following a D&C procedure that includes a thorough clinical examination and a detailed ultrasound assessment. Healthcare providers should not overlook the diagnosis of omentum involvement in the presence of a history of intrauterine procedures.

Histological and immunohistochemical study of brain damage in traumatic brain injuries in children, depending on the survival period.

Numerous studies showed that, at present, traumatic brain injury (TBI) is one of the main causes of death in young adults, but also a main cause of disabilities at all ages. For these reasons, TBI are continuously investigated. In our study, we evaluated the histopathological (HP) and immunohistochemical (IHC) changes that occurred in the brain in underage patients after a severe TBI depending on the survival period. We histopathologically and immunohistochemically analyzed a number of 22 cases of children, deceased in Dolj County, Romania, following some severe TBI, undergoing autopsy within the Institute of Forensic Medicine in Craiova between 2015-2020. Patients were divided into three groups depending on the survival period, namely: (i) patients who died during the first 24 hours of the accident; (ii) patients who died after seven days of survival; (iii) patients who died after 15 days of survival. Microscopic examinations of the brain fragments, collected during the necropsy examination, showed that the traumatic agent caused primary injuries in all brain structures (cerebral parenchyma, meninges, blood vessels). However, HP injuries ranged in size and intensity from one area to another of the brain. In patients with a longer survival period, there was observed the presence of smaller primary injuries and larger secondary injuries. There was also observed a growth in the number of meningo-cerebral microscopic injuries, depending on the increase of the survival period.

Intrauterine Transmission of Hepatitis C Virus Concomitant with Isolated Severe Fetal Ascites.

BACKGROUND: Perinatal Hepatitis C Virus (HCV) transmission occurs in 4-7% of the cases with detectable viremia at delivery. HCV testing in pregnancy is recommended. The fetal infection was previously described as asymptomatic although there are two cases, including this one, to report the presence of isolated fetal ascites in HCV infected fetuses. CASE REPORT: A 42-year-old patient, 3G, 3P, presented in the Emergency Room for painful uterine contraction. The third-trimester ultrasound examination noted severe fetal ascites, accompanied by hyperechoic bowels and polyhydramnios. The diagnosis required a detailed ultrasound exam, invasive testing (amniocentesis, cordocentesis, and fetal paracentesis), and a complete workup. The mother tested positive for HCV antibodies, and the fetal cord blood tested positive for HCV RNA. The ascites resolved after paracentesis, and the gastrointestinal and respiratory functions markedly improved. The fetus was delivered at term in good condition. CONCLUSIONS: The etiology of isolated fetal ascites is broad. This case may indicate that intrauterine HCV transmission is a potential cause of isolated fetal ascites in the absence of other explanation, and isolated fetal ascites can be the only sign revealed on a routine examination. We suspected, having no other detected cause for ascites, the intrauterine transmission of HCV. Invasive procedures, such as paracentesis, are required for abdominal decompression to manage isolated fetal ascites, as it may be a saving procedure. A genetic investigation is needed, and a good neonatal outcome is expected in the absence of fetal structural or genetic abnormalities, as in our case.

Extrapulmonary Gastrointestinal Presentation of Coronavirus (COVID-19): A Case Report and Review of Literature.

Coronavirus disease 2019 (COVID-19) is currently the causative agent for a global health emergency and is predominantly associated with respiratory symptoms. In this case, a patient presented to the emergency department with gastrointestinal symptomatology without associated respiratory findings and was subsequently diagnosed with COVID-19 based on incidental findings from an abdominal computed tomography (CT) study. Given the patient's lack of respiratory symptoms, diagnosis and treatment were ultimately delayed. During this global health crisis, an improved understanding of the various presentations of COVID-19 is paramount in an effort to initiate immediate treatment and prevent further transmission.

Correlations Between the Glasgow Score and the Survival Period in Patients with Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) contributes by 30% to the mortality induced by traumatic injuries, also being one of the major causes of invalidity worldwide. The clinical classification of the severity of mild, moderate or severe TBI is made according to the Glasgow scale, according to the patient's conscious state, motric changes, speech changes and eye opening. In our study, we evaluated the correlation between the Glasgow score at admission and the survival period of patients suffering from TBI, using the data recorded in the Forensic Medicine Institute of Craiova between 2011-2017 on 1005 cases with the diagnosis of death by TBI. We observed that TBI affects persons of all ages, starting from babies up to the elderly aged over 90 years old. Regarding the generation mechanism, most deaths were caused by fallings (438 cases, 43.58%), followed by car accidents (333 cases, representing 33.13%). The number of patients who presented a post-traumatic survival period was 802 (79.80%), of which 779 adults (77.51%) and 23 children (2.29%). Among these, 785 (78.11%-764 adults and 21 children) were hospitalized, while in 64.58% of the TBI patients there was recorded the Glasgow score at admission. 75% of the TBI patients in whom there was recorded the Glasgow score presented a 1st-4th coma degree, with a Glasgow score from 3 to 8 and only 25% had a slightly altered or preserved conscious state, with a Glasgow score=9-15. The survival period varied from less than 24 hours to over 15 days. In the hospitalized patients, there were performed emergency surgeries in 269 (26.76%) cases, the surgical intervention being temporized in 108 (10.74%) patients.

Severe traumatic brain injury (TBI) - a seven-year comparative study in a Department of Forensic Medicine.

Deaths caused by traumatic brain injury (TBI) increase in incidence every year worldwidely, mainly in developing countries. Thus, World Health Organization (WHO) estimates that in 2020, TBI will become the third main cause of death. In our study, we evaluated the deaths caused by TBI recorded within the Institute of Forensic Medicine of Craiova, Romania, between 2011 and 2017. Therefore, according to age, the cases were divided into two groups: people aged 0-18 years old (including 18 years old) and people aged over 18 years old (a total of 1005 cases, of which 971 were adults and 34 included in the age group 0-18 years old). In both groups, most patients were males from the rural area. In adults, falling was the main legal entity of the cases, followed by car accidents (which were the most common in children). In both groups, in car accidents, most of them were pedestrians and car occupants. Various aggressions (human, animal, self-injury) were found in 94 (9.68%) of the adult cases and in four (11.76%) cases of children. Another parameter under study was the blood alcohol concentration, being observed that most of the subjects with positive blood alcohol content died from car accidents. By evaluating the Glasgow Coma Scale (GCS) score as a prognostic factor, most of the subjects presented third and fourth degree coma at admission; still, 5.14% of the adult patients who deceased had GCS score 15 at admission, death occurring probably by developing some intracranial hematomas in time. Regarding the morphology of the lesions, most patients presented various forms of cranial fractures, 185 (19.05%) adults in association with extradural hemorrhages∕hematomas, but also there were four cases with extradural hematomas without any cranial fractures. In children, there was highlighted a single case of extradural hemorrhage under the fracture line. Seventy-eight percent of the adults and 44.12% of children presented subdural hematomas associated with other meningo-cerebral lesions. Also, 83.63% of the adults and 97% of children presented brain contusions. In both groups, brain laceration was observed in approximately 50% of the cases.

Experimental model for the study of traumatic brain injury.

Traumatic brain injury (TBI) represents a public healthcare problem and a major economic burden, all over the world. It is estimated that every year, on the globe, there occur about two million severe TBI and over 42 million mild TBI. The main causes of TBI in civil population are fallings, followed by car accidents. In the last decades, the accelerated development of car industry and the poor development of traffic infrastructure in low- and average-income countries led to an increasing number of brain injuries, this becoming a major problem for medical health systems. According to some studies, approximately 1.35 million people die every year because of car accidents. In the last four decades, these types of injuries started to be studied in order to understand the lesion mechanisms for developing new safety equipment that may be installed on vehicles. The device presented by us for causing a TBI in a lab rat (mechanical pendulum) allows the performance of several major types of TBI, according to the kinetic energy, exposure area, contact surface, etc. The impact energies obtained by the device we presented may vary on a large scale, from less than 1 J up to 10 J, according to its weight, launching angle and impact head shape, thus being obtained minor, moderate or severe TBI.

Complex evaluation in patients with knee osteoarthritis.

Knee osteoarthritis (KOA) is a very common, slowly progressive and incurable articular disease resulting in the breakdown of cartilage and bone in the joint, which causes significant discomfort, pain and disability, with a significant socio-economic impact. The aim of our observational study for patients with symptomatic KOA was to investigate the changes of C-terminal telopeptide of type II collagen (CTX-II) in serum pre and post a complex rehabilitation program and to establish the correlation between all studied parameters [clinical, functional, serum CTX-II (sCTX-II) and histological aspects obtained through arthroscopy]. During 2016-2017, we performed an observational study including 24 patients, between 59 and 76 years old, diagnosed with KOA. Studied patients were completely assessed before (T1) and four months after a complex rehabilitation program (T2). The measured parameters were stiffness, pain, and physical function and we used the Visual Analogue Scale (VAS) for pain, with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), sCTX-II value obtained by enzyme-linked immunosorbent assay (ELISA) test, histological assessment of knee cartilage after arthroscopy. In the histological assessment of our patients, we observed that the cells of the superficial areas were round and hypertrophic, the cartilage tissue had few proteoaminoglycans and glycosaminoglycans, with an airy aspect of the matrix and degenerate cells, numerically reduced. After positive diagnosis, the complete treatment, including the rehabilitation program, seems to be the ideal option for improving the CTX-II values, as well as the quality of life in KOA patients.

Liver hydatid cyst - cause of violent death. Case presentation.

Liver hydatid cyst represents one of the most frequent localizations of Echinococcus granulosus tapeworm in humans. The disease progresses symptom-free in most patients, due to a slow growth rhythm of the cyst. When it reaches large sizes, the hydatid cyst causes discomfort or pain in the liver bed, low appetite, phenomena of hepatitis or cholangitis. The patients are most often diagnosed with liver hydatid cyst after imagistic investigations (radiological or ultrasound) for symptoms that, most commonly, are not related to a hydatid cyst. We present the case of an 11-year-old girl, with no pathological history, who presented forme fruste symptoms, not acknowledged by her parents, and deceased after an anaphylactic shock caused by the rupture of a liver hydatid cyst.

Evaluation of brain injuries in children deceased due to head trauma.

Traumatic brain injuries (TBIs) present an ever-growing prevalence, especially in the developing countries. Although 80-95% are mild to average injuries, they determine multiple severe neurological sequelae and disabilities. Most of these injuries are caused by traffic accidents. We studied a number of 29 cases of severe TBIs, in children who deceased immediately or after a few days of survival. Most of them (over 68%) were caused by traffic accidents. The incidence of traumas increased by age, most cases being recorded in the age group 10-15 years old. The TBIs were complex ones. In 86.21% of the cases, the forensic examination highlighted the presence of cranial fractures; in 93% of the cases, there were highlighted complex meningo-cerebral injuries: leptomeningeal hemorrhage associated with brain contusion injuries and with intraventricular blood flood, as well as destructive lesions of brain dilaceration; only in 7% of the cases there were highlighted meningeal lesions, with no brain lesions. The severity of the brain injuries was quite varied, according to the force of the cause agent. The histopathological and immunohistochemical examinations showed that the severity of TBIs increased according to the survival time, by adding secondary lesions caused by brain ischemia and local inflammatory reaction.

Clinico-statistical and morphological aspects of severe traumatic brain injuries.

Traumatic brain injuries (TBIs) represent a problem of public health all over the world if we consider its incidence, mortality and the big social costs. The increase of road and train traffic, the development of industry, the growth of alcohol consumption, the emergence and increase of terrorist attacks have led to more frequent and severe TBIs. There were registered 3260 deaths at the Institute of Forensic Medicine in Craiova, Romania, between 2010 and 2014; they were the result of severe traumas, 622 (19.07%) being caused by TBIs. The most affected by TBIs were men (the men÷women ratio was of 3÷1) and the elderly, mainly in the rural area. The main risk factor was alcohol intake; about 44% of the deceased people were under alcohol influence. The forensic examination highlighted the severity of cerebral meningeal lesions, the most frequent being cerebral and vascular lesions. The histopathological and immunohistochemical examinations emphasized various microscopic changes in accordance with the severity of the trauma and the time passed from impact until death.

Stillbirth in dichorionic twins discordant for major and minor anomaly, followed by asynchronous delivery - a rare occurrence. Case presentation.

The single stillbirth long-term intrauterine retention in dichorionic twin pregnancy is rarely reported. Also, the birth of a fetus is followed in most cases by immediate expulsion of the second twin. We hereby present an unusual case of asynchronous delivery of dichorionic twins, associating discordance for major and minor anomaly. The intrauterine death of the twin A, presenting a large sacrococcygeal tumor, occurred in the second trimester. The deceased twin A was born at 29 weeks' gestational age (GA). The twin B was extracted by Caesarean section at 31 weeks and had a good outcome. We performed a close follow-up of the high-risk pregnancy and we used tocolytic and antibiotic drugs for prolonging it. Corticoid therapy was administered for the lung maturation of the second twin. The expectant management in the single twin stillbirth dichorionic pregnancy and the asynchronous delivery had a significant impact on the newborn outcome.

Ethical issues in therapeutic endoscopy - can communication between patient and physician make a difference?

Therapeutic endoscopy represents a major step in evidence-based medicine with great potential in the evolution of non-invasive surgery. The evolutionary status of endoscopy has reached a level where some of the surgical intervention can be performed in a minimal invasive way, with great benefits for the patient. However, this rises up some ethical issues regarding the patient's comfort zone, possible risks and complications and subjected the physician to possible litigation situations if not well trained. A rather good interaction and communication between patient and endoscopist is mandatory, as the health-care experience might be more satisfying. Unfortunate situations may also be avoided if intensive training and up to date knowledge and skills are acquired before jumping to therapeutic endoscopy. The continuous development and general focus on interventional endoscopy seems to have a key role on current medical standings. Therefore, in the following paper we have tried to underline the potential ethical problems that both the patient and the physician should take into consideration towards a better therapeutic endoscopic result.

Strongyloidiasis and diffuse alveolar hemorrhage in a patient with systemic lupus erythematosus.

The presence of Strongyloides stercoralis infection in patients with systemic lupus erythematosus (SLE) has been described previously. Strongyloides stercoralis hyperinfection syndrome (SHS) that usually develops in patients under immunosuppressive therapy may affect a variety of organs, but the presentation with diffuse alveolar hemorrhage (DAH) is rare with only a few cases described in the literature. We present the case of a 36-year-old Hispanic female with a past medical history relevant for SLE and a recent diagnosis of lupus nephritis and hypertension. The patient who developed sudden and progressive abdominal pain and respiratory distress, with the presence of bilateral crackles and severe hypoxemia, is currently under treatment with steroids and cyclophosphamide for worsening of lupus nephritis. The patient underwent endotracheal intubation and mechanical ventilation, and computed tomography showed the presence of bilateral pulmonary infiltrates suggestive of DAH. Bronchoalveolar lavage was done and showed the presence of filariform larvae, morphologically consistent with Strongyloides stercoralis. Treatment with ivermectin was started and patient responded to treatment with improvement of clinical status. In conclusion, the development of SHS in patients with lupus, especially when receiving immunosuppressive therapy, is a severe and potentially fatal complication. Early detection and treatment may decrease mortality.

Methotrexate induced pancytopenia.

The well-reported methotrexate (MTX) toxicities are based on the duration and cumulative dosing of drug. The typical toxicities can be predicted by the timing of drug administration, where mucositis occurs as an earlier effect, while myelosuppression and the sequelae of pancytopenia occur later after MTX administration. Despite these well-known toxicities, low dose MTX therapy can become problematic, in particular with the elderly, who are at a greater risk for significant myelosuppression. We present a case of a 73-year-old female with pancytopenia causing severe neutropenia, mucocutaneous bleeding, and bruising and requiring intravenous antibiotic therapy and limited transfusion dependence as a result of low dose daily MTX for rheumatoid arthritis.