Project description:Bullous pemphigoid (BP) is a rare, life-threatening autoimmune blistering disease with pruritus and tension blisters/bullous as the main clinical manifestations. Glucocorticosteroids are the main therapeutic agents for it, but their efficacy is poor in some patients. Tofacitinib, a small molecule agent that inhibits JAK1/3, has shown incredible efficacy in a wide range of autoimmune diseases and maybe a new valuable treatment option for refractory BP. To report a case of refractory BP successfully treated with tofacitinib, then explore the underlying mechanism behind the treatment, and finally review similarities to other cases reported in the literature. Case report and literature review of published cases of successful BP treatment with JAK inhibitors. The case report describes a 73-year-old male with refractory BP that was successfully managed with the combination therapy of tofacitinib and low-dose glucocorticoids for 28 weeks. Immunohistochemistry and RNA sequencing were performed to analyze the underlying mechanism of tofacitinib therapy. A systematic literature search was conducted to identify other cases of treatment with JAK inhibitors. Throughout the 28-week treatment period, the patient experienced clinical, autoantibody and histologic resolution. Immunohistochemical analysis showed tofacitinib significantly decreased the pSTAT3 and pSTAT6 levels in the skin lesions of this patient. RNA sequencing and immunohistochemical testing of lesion samples from other BP patients identified activation of the JAK-STAT signaling pathway. Literature review revealed 17 previously reported cases of BP treated with four kinds of JAK inhibitors successfully, including tofacitinib (10), baricitinib (1), upadacitinib (3) and abrocitinib (3). Our findings support the potential of tofacitinib as a safe and effective treatment option for BP. Larger studies are underway to better understand this efficacy and safety.
Project description:Background: One of the most serious complications of cranial radiotherapy is the development of radiation-induced glioma, which is estimated to occur in 1 to 4% of patients who have received cranial irradiation and has a worse prognosis than sporadic glioblastoma. To date, owing to its rarity, no standard of care has been established for radiation-induced glioma. Although comprehensive genetic analysis has recently uncovered the molecular characteristics of radiation-induced glioma, the full picture remains unclear, and the molecular features associated with treatment response and prognosis are poorly understood. Case presentation: A 45-year-old man presented with generalized seizures caused by multiple brain tumors involving the right frontal lobe, thalamus, and brainstem. The patient had a history of whole-brain radiotherapy for the recurrence of Burkitt's lymphoma at the age of 12. He underwent craniotomy, and the histological diagnosis was a high-grade glioma with isocitrate dehydrogenase-wildtype, which was presumed to be a radiation-induced glioma that developed 33 years after whole-brain irradiation. The Heidelberg DNA-methylation brain classifier most closely matched diffuse pediatric-type high-grade glioma, receptor tyrosine kinase-1 subtype, which is a typical methylation class of radiation-induced glioma. Methylation-specific polymerase chain reaction showed that the O6-methylguanine-DNA methyltransferase gene promoter was unmethylated. Next-generation sequencing identified CDKN2A/B deletion as well as co-amplification of several receptor tyrosine kinase-encoding genes including PDGFRA, KIT, and KDR, which are all located on chromosome 4q12. Amplification of this region is present broadly across cancers and is associated with a poor prognosis in sporadic glioblastoma. Nevertheless, the patient received conventional chemoradiotherapy with temozolomide. Subsequent multimodal imaging with magnetic resonance imaging and 11C-methionine positron emission tomography revealed complete remission of all lesions. Two years later, the patient is currently alive with a favorable performance status. Conclusions: Despite radiation-induced glioma with molecular features suggestive of an aggressive phenotype, our patient unexpectedly responded well to conventional chemoradiotherapy, resulting in complete remission that is exceptional in sporadic glioblastoma. Our case indicates that some of the radiation-induced gliomas may have distinct molecular characteristics involved in the therapeutic response that differ from those of sporadic glioblastomas.
Project description:Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical.A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients.The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).
Project description:In clinical use, bevacizumab has improved the overall survival (OS) and progression-free survival (PFS) of malignant solid tumors, and the safe use of bevacizumab has gradually become the mainstream direction of clinical, nursing and pharmaceutical research. Bevacizumab is a humanized anti-VEGF drug. By binding to VEGF, it loses the opportunity to activate VEGFR and then plays an anti-angiogenic role. In addition, more and more studies have emphasized the efficacy and safety of bevacizumab in the treatment of brain metastases from solid tumors. Bevacizumab has its advantages in terms of crossing the blood-brain barrier, increasing radiosensitivity, and reducing radiation-induced brain edema. However, VEGF can maintain the normal function of vascular endothelial cells. Blocking the VEGF pathway can lead to endothelial dysfunction, and the anti-VEGF mechanism of bevacizumab will inevitably lead to a series of thrombotic events and bleeding events. This study reported six cases of cerebrovascular accidents, including ischemic stroke and cerebral hemorrhage, after bevacizumab use. At the same time, this study reviewed the related studies of cardiovascular and cerebrovascular accidents caused by bevacizumab, and analyzed the management of such bevacizumab-related adverse events. We put forward our own views on the early identification and long-term management of adverse events, as well as the subsequent reuse of bevacizumab, hoping to provide more basis for the management of clinical bevacizumab application.
Project description:We report a case of a 55 years old women who present a ALK associated renal cell carcinoma, with 3p deletion and measling of TFE3 expression. With CGH analysis and FISH we identify the rearrangment of ALK with TPM3
Project description:Oxaliplatin has become a widely used agent in neoadjuvant chemotherapy for gastrointestinal tract tumors and is an integral part of the therapeutic approach for managing colorectal cancer recurrences and metastases, resulting in a more favorable prognosis for patients. Nevertheless, oxaliplatin can give rise to idiopathic non-cirrhotic portal hypertension (INCPH). The emergence of INCPH can disrupt tumor chemotherapy and incite persistent adverse reactions in later stages, significantly complicating clinical management. Consequently, we have presented a case report of INCPH induced by oxaliplatin chemotherapy with the aim of advancing the diagnosis and treatment of this condition, with a particular focus on the clinical manifestations. This study has ascertained that the condition is primarily attributed to complications related to portal hypertension, such as gastrointestinal bleeding, splenomegaly, and hypersplenism. The pathological features primarily involve hepatic sinus dilation and congestion, portal obstruction, absence, stenosis, shunting, localized venous and perisinusoidal fibrosis, as well as hepatocellular atrophy. Treatment primarily concentrates on strategies typically employed for cirrhosis. Endoscopic ligation, sclerotherapy, and non-selective beta-blockers (NSBBs) can be selected to prevent and treat variceal hemorrhage. Transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation can also be chosen for severe cases. Notably, despite the timely discontinuation of oxaliplatin, most patients continue to experience disease progression, ultimately resulting in a poor prognosis due to either tumor advancement or the ongoing progression of portal hypertension. This emphasizes the importance for physicians to be aware of and consider the risk of INCPH when prescribing oxaliplatin.
Project description:IntroductionVarious classes of antibiotics have been linked to causing a wide range of neuropsychiatric symptoms. These manifestations range from psychosis and delirium to encephalitis and intracranial hypertension. The prevalence of psychosis adverse drug reactions (ADRs) for individual antibiotics ranges from 0.3 to 3.8%. We report a rare case of linezolid-induced psychosis and hallucination.Case presentationWe report a 52-year-old Asian gentleman who presented with an altered level of consciousness and hallucinations. He was treated for third-degree burns of 31% of the body for two months. Based on clinical and laboratory investigations, linezolid-induced psychosis and hallucination were diagnosed. His Naranjo probability score was +8. The drug was stopped, and the patient recovered successfully.ConclusionOn rare occasions, toxic blood levels of linezolid can lead to neuropsychiatric manifestations. Both linezolid-induced psychosis and hallucinations are manageable by suspension of the drug. Therefore, physicians should monitor the blood levels of this antibiotic to keep their patients safe from such serious adverse effects.
Project description:BackgroundDoxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment. The use of anthracycline is limited by dose-dependent cardiotoxicity, which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure. Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents, there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity (AIC).Case summaryA 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70% determined by transthoracic and dobutamine stress echocardiogram. She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery, and received a total of 450 mg/m2 doxorubicin at the end of her treatment course. She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms. Approximately two months after her last chemotherapy, the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure. Echocardiogram showed an ejection fraction of 5%-10% with severe biventricular failure. Despite attempts to optimize cardiac function, the patient's hemodynamic status continued to decline, and resuscitation was not successful on the seventh day of hospitalization. The autopsy showed no evidence of osteosarcoma, and the likely cause of death was cardiac failure with the evidence of pulmonary congestion, liver congestion, and multiple body cavity effusions.ConclusionWe present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo. Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice. We have reviewed literature and recent advances in the prediction and prevention of AIC. Although risk factors currently identified can help stratify patients who need closer monitoring, there are limitations to our current understanding and further research is needed in this field.
Project description:BackgroundPaclitaxel is a chemotherapeutic agent commonly used for ovarian, lung, breast carcinoma, and Kaposi's sarcoma. Its common side effects include hypersensitivity reaction, bone marrow suppression, and peripheral neuropathy. However, a rare and life-threatening side effect is paclitaxel-induced myocardial infarction.Case presentationA 71-year-old man with type 2 diabetes mellitus, hypertension, heavy smoking history, previous coronary artery disease with percutaneous coronary intervention (PCI) in left anterior descending artery (LAD), and non-small lung cancer presented with non-ST elevation myocardial infarction during infusion of paclitaxel infusion. Coronary angiogram showed de novo three vessel disease with 70% stenosis in ostial to distal left main artery (LM) and 80% in-stent re-stenosis in proximal to mid left anterior descending artery.ConclusionsPhysicians should be keeping this in mind when dealing with patients on paclitaxel, especially if they have previous risk factors for coronary artery disease.