Neuroimaging Assessment of Aggressive Pituitary Adenomas

Aggressive pituitary adenomas (APA) are adenomas that show rapid growth, invasiveness, frequent or multiple relapses, or are resistant to conventional therapies. Clinical-imaging assessment of aggressive pituitary adenomas with the aid of magnetic resonance imaging (MRI) plays an important role in early prediction, further disease outcomes and aggressive behavior of adenomas. Purpose of the Study: was to assess the correlation of neuroimaging data with the hormonal activity of APA. Materials and Methods: The study included 74 patients with aggressive pituitary adenomas. The average age of the patients was from 12 to 69. The patients underwent a basal assessment of the level of pituitary hormones: prolactin (PRL), GH (growth hormone), insulin-like growth factor-1 (IGF-1) and blood cortisol by the RIA method, as well as an MRI study. Knop's classification was used to assess the invasion. Results: The hormonal workup showed prevalence of inactive pituitary adenomas among aggressive adenomas. No correlation was found between the hormonal activity of aggressive adenomas and the volume of pituitary adenomas. Moreover, MRI data indicated that invasion into the cavernous sinus of the III degree and heterogeneity of the adenoma may be considered equivalents of aggressiveness. Conclusion: The established patterns support the need for visualization assessment of aggressive pituitary adenomas and strongly suggest the evaluation of the degree of aggression based on tumor heterogenecity, chiasm compression, hypo- and iso-intensity in T1 mode and hyperintensity in T2 modes.

Recurrent Anti-AMPA Receptor Limbic Encephalitis: A Case Report and Literature Review

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is a relatively rare anti-neuronal surface antigen autoimmune encephalitis (LE). We described a case of a 47-year-old Chinese man having anti-AMPA receptor limbic encephalitis initially presented with cognitive decline, undetectable antibodies, and normal imaging findings in magnetic resonance image (MRI) and then developed into typical autoimmune limbic encephalitis a few months later with a course of multiple relapses. In addition, we found progressive brain atrophy in our case, which was a rare presentation of LE. This report also summarized the characteristics of nine reported cases of anti-AMPA receptor limbic encephalitis with relapse up to date. This case highlighted that autoimmune limbic encephalitis is an important differential diagnosis for patients with typical symptoms even when the MRI and antibodies are normal, and more attention should be paid to the relapse of anti-AMPA receptor encephalitis.

Management of Persistent SARS-CoV-2 Infection in Patients with Follicular Lymphoma

Introduction: There is no consensus on the management of the coronavirus disease (COVID-19) in patients with secondary immunosuppression due to either an underlying haematological disease or to the effects of immunochemotherapy (ICT). Some of them may present persistent infection with multiple relapses of the COVID-19, requiring several admissions. This study evaluated the clinical characteristics and outcomes after treatment of five patients with follicular lymphoma (FL), previously treated with ICT, who developed several episodes of COVID-19. Methods: We analyzed the clinical evolution and response to treatment with antiviral agent, steroids and convalescent plasma in five patients with FL and SARS-CoV-2 persistent infection. Reverse-transcriptase-polymerase-chain-reaction (RT-PCR) tests and peripheral blood immunophenotype were performed for all patients. Results: All patients required hospitalization due to pneumonia with severity criteria and were re-admitted after a median of 22 days (13-42) from the previous discharge. They all showed B-cell depletion by immunophenotyping and no traces of immunoglobulin (IgG) antibodies against SARS-CoV-2 were detected in any of the cases. The survival rate was 80%. Conclusion: The combination therapy evidenced clinical benefits, demonstrating its capacity to control infection in immunosuppressed follicular lymphoma patients treated with ICT.

Antibodies in Serum and MENSA Predict Non-recurrence in Primary Clostridioides difficile infection.

Background: Within eight weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no validated biomarkers predictive of recurrence during primary infection. This study demonstrates the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence. Methods: Forty-six hospitalized CDI patients were enrolled at Emory University Hospitals. Serum and MENSA samples prepared during weeks 1, 2, and 4 following symptom-onset were measured for antibodies specific for ten C. difficile antigens.Results: Among the 46 C. difficile-infected patients, nine (19.5%) experienced recurrence within eight weeks of primary infection. Among the 37 non-recurrent patients, 23 had anti-C. difficile MENSA antibodies specific for any of the three toxin antigens: TcdB-CROP, TcdBvir-CROP, and/or CDTb. Positive MENSA responses occurred within the first week post-symptom onset, including six patients who never seroconverted. A similar trend was observed in serum responses, but they peaked later and identified fewer patients (19/37). In contrast, none of the patients who subsequently recurred after hospitalization produced antibodies specific for the three C. difficile toxin antigens. IgA antibodies for the toxin antigens demonstrated the greatest predictive power for protection from recurrence. Discussion: The development of IgG and/or IgA antibodies for three C. difficile toxins in serum and/or MENSA has prognostic potential. These immunoassays measure nascent immune responses that reduce the likelihood of recurrence. Early identification of patients at-risk for recurrence can reduce costs and morbidity.

Infective endocarditis in intravenous drug abusers: clinical challenges emerging from a single-centre experience

Background Intravenous drug abuse (IDA) is a known risk factor for infective endocarditis (IE) and is associated with frequent relapses, but its prognostic impact is still debated. The potential futility of surgery in this population is a further issue under discussion. We aimed to describe the clinical characteristics, the therapeutic strategy, and the prognosis associated with IDA in IE. Methods We retrospectively analysed 440 patients admitted to a single surgical centre for definite active IE from January 2012 to December 2020. Results Patients reporting IDA (N = 54; 12.2%) were significantly younger (p < 0.001) and presented fewer comorbidities (p < 0.001). IDA was associated with a higher proportion of relapses (27.8 vs. 3.3%, p < 0.001) and, at multivariable analysis, was an independent predictor of long-term mortality (HR 2.3, 95%CI 1.1–4.7, p = 0.015). We did not register multiple relapses in non-IDA patients. Among IDA patients, we observed 1 relapse after discharge in 9 patients, 2 relapses in 5 patients and 3 relapses in 1 patient. In IDA patients, neither clinical and laboratory variables nor the occurrence of even multiple relapses emerged as indicators of an adverse risk–benefit ratio of surgery in patients with surgical indication. Conclusions IE secondary to IDA affects younger patients than those with IE not associated with IDA. Probably due to this difference, IE secondary to IDA is not associated with significantly higher mortality, whereas the negative, long-term prognostic impact of IDA emerges in multivariate analysis. Considering the good prognosis of patients with uncomplicated IE treated medically, surgery should be reserved to patients with a strict- guidelines-based indication. However, since there are no clear predictors of an unfavourable risk–benefit ratio of surgery in patients with surgical indication, all patients with a complicated IE should be operated, irrespective of a history of IDA.

Increased primaquine total dose prevents Plasmodium vivax relapses in patients with impaired CYP2D6 activity: report of three cases

Background The relapsing nature of Plasmodium vivax infection is a major barrier to its control and elimination. Factors such as adequate dosing, adherence, drug quality, and pharmacogenetics can impact the effectiveness of radical cure of P. vivax and need to be adequately evaluated. CYP2D6 pathway mediates the activation of primaquine (primaquine) into an active metabolite(s) in hepatocytes, and impaired activity has been linked to a higher risk of relapse. Cases presentation Three patients diagnosed with P. vivax malaria presented repeated relapses after being initially treated with chloroquine (25 mg/kg) and primaquine (3.5 mg/kg in 14 days) at a non-endemic travel clinic. Recurring episodes were subsequently treated with a higher dose of primaquine (7 mg/kg in 14 days), which prevented further relapses in two patients. However, one patient still presented two episodes after a higher primaquine dose and was prescribed 300 mg of chloroquine weekly to prevent further episodes. Impaired CYP2D6 function was observed in all of them. Conclusion Lack of response to primaquine was associated with impaired CYP2D6 activity in three patients presenting multiple relapses followed in a non-endemic setting. Higher primaquine dosage was safe and effectively prevented relapses in two patients and should be further investigated as an option in Latin America. It is crucial to investigate the factors associated with unsuccessful radical cures and alternative therapeutic options.

Effectiveness of Caplacizumab Nanobody in Acquired Thrombotic Thrombocytopenic Purpura Refractory to Conventional Treatment

Acquired thrombocytopenic thrombotic purpura (aTTP) is an autoantibody-mediated disease against the enzyme A Disintegrin and Metalloprotease domain with ThromboSpondin-1 type motif 13, which until now has been treated with plasma exchange (PEX) and corticosteroids. A 29-year-old female patient, who presented with aTTP in the context of pregnancy, has developed multiple relapses after treatment with PEX, corticosteroids, and rituximab. Recently, caplacizumab, a nanobody against von Willebrand factor, has been approved for the treatment of aTTP. In our patient, caplacizumab achieved better disease control, with a lower platelet count restoration time, days of PEX and hospitalization duration, as compared to standard therapy, reproducing the results of clinical trials. Caplacizumab represents a significant advance in the treatment of aTTP, especially in cases of recurrent relapses.

Parosteal Osteosarcoma with Pancreatic Metastasis and Multiple Relapses: A Case Report and Review of the Literature

Osteosarcoma is the most common primary bone cancer in all age groups. Metastasis mostly occurs with high-grade tumors disseminating to the lungs and other bones. Spread to the pancreas is rare and undocumented in the low-grade subtypes. Additionally, it is uncommon for the disease course of low-grade subtypes to involve multiple relapses. We present a 35-year-old woman with parosteal osteosarcoma who has experienced an atypical metastasis to the pancreas as well as multiple local and pulmonary relapses. The lesion was identified incidentally on routine imaging, and the patient underwent resection. We compare our case to the other reports of pancreatic metastasis in the literature. Despite being especially rare, clinicians ought to be aware of pancreatic metastasis of osteosarcoma. Furthermore, despite parosteal osteosarcoma’s less aggressive disease course, it can uncommonly lead to multiple relapses. We present a rare case exemplifying these phenomena in the prognostically favorable histologic subtype of parosteal osteosarcoma.

Research advances on the immune research and prospect of immunotherapy in pituitary adenomas

Background Pituitary adenomas are one type of intracranial tumor, which can be divided into microadenoma (≤ 1 cm), macroadenoma (> 1 cm), and giant adenoma (≥ 4 cm) according to their diametral sizes. They are benign, typically slow-progressing, whereas the biological behavior of some of them is invasive, which presents a major clinical challenge. Treatment of some pituitary adenomas is still difficult due to drug resistance or multiple relapses, usually after surgery, medication, and radiation. At present, no clear prediction and treatment biomarkers have been found in pituitary adenomas and some of them do not cause clinical symptoms, so patients are often found to be ill through physical examination, and some are even found through autopsy. With the development of research on pituitary adenomas, the immune response has become a hot spot and may serve as a novel disease marker and therapeutic target. The distribution and function of immune cells and their secreted molecules in pituitary adenomas are extremely complex. Researchers found that infiltration of immune cells may have a positive effect on the treatment and prognosis of pituitary adenomas. In this review, we summarized the advance of tumor immunity in pituitary adenomas, revealing the immunity molecules as potential biomarkers as well as therapeutic agents for pituitary adenomas. Conclusion The immune studies related to pituitary adenomas may help us find relevant immune markers. At the same time, the exploration of immunotherapy also provides new options for the treatment of pituitary adenomas.