A novel neuroprotective method against ischemic stroke by accelerating the drainage of brain interstitial fluid.

Ischemic stroke is a leading cause of death and disability worldwide. Inflammatory response after stroke determines the outcome of ischemic injury. A recent study has reported an efficient method, epidural arterial implantation (EAI), for accelerating interstitial fluid (ISF) drainage, which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space (ECS). In this study, the method of EAI was modified (m-EAI) to control its function of accelerating the ISF drainage at different time points following ischemic attack. The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion (tMCAO) rat model. The results demonstrated the accumulation of IL-1ß, IL-6, and TNF-α was significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats, accompanied with decreased infarct volume and improved neurological function. This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS. Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.

PSMA-PET follow-up to assess response in patients not receiving PSMA therapy: Is there value beyond localization of disease?

Introduction: Prostate Specific Membrane Antigen Positron Emission Tomography (PSMA-PET) is routinely used for the staging of patients with prostate cancer, but data on response assessment are sparse and primarily stem from metastatic castration-resistant prostate cancer (mCRPC) patients treated with PSMA radioligand therapy. Still, follow-up PSMA-PET is employed in earlier disease stages in case of clinical suspicion of disease persistence, recurrence or progression to decide if localized or systemic treatment is indicated. Therefore, the prognostic value of PSMA-PET derived tumor volumes in earlier disease stages (i.e., hormone-sensitive prostate cancer (HSPC) and non-[177Lu]Lu-PSMA-617 (LuPSMA) therapy castration resistant prostate cancer (CRPC)) are evaluated in this manuscript. Methods: A total number of 73 patients (6 primary staging, 42 HSPC, 25 CRPC) underwent two (i.e., baseline and follow-up, median interval: 379 days) whole-body [68Ga]Ga-PSMA-11 PET/CT scans between Nov 2014 and Dec 2018. Analysis was restricted to non-LuPSMA therapy patients. PSMA-PETs were retrospectively analyzed and primary tumor, lymph node-, visceral-, and bone metastases were segmented. Body weight-adjusted organ-specific and total tumor volumes (PSMAvol: sum of PET volumes of all lesions) were measured for baseline and follow-up. PSMAvol response was calculated as the absolute difference of whole-body tumor volumes. High metastatic burden (>5 metastases), RECIP 1.0 and PSMA-PET Progression Criteria (PPP) were determined. Survival data were sourced from the cancer registry. Results: The average number of tumor lesions per patient on the initial PET examination was 10.3 (SD 28.4). At baseline, PSMAvol was strongly associated with OS (HR 3.92, p <0.001; n = 73). Likewise, response in PSMAvol was significantly associated with OS (HR 10.48, p < 0.005; n = 73). PPP achieved significance as well (HR 2.19, p <0.05, n = 73). Patients with hormone sensitive disease and poor PSMAvol response (upper quartile of PSMAvol change) in follow-up had shorter outcome (p < 0.05; n = 42). PSMAvol in bones was the most relevant parameter for OS prognostication at baseline and for response assessment (HR 31.11 p < 0.001; HR 32.27, p < 0.001; n = 73). Conclusion: PPP and response in PSMAvol were significantly associated with OS in the present heterogeneous cohort. Bone tumor volume was the relevant miTNM region for OS prognostication. Future prospective evaluation of the performance of organ specific PSMAvol in more homogeneous cohorts seems warranted.

Erosive lesion of the nipple: What is your diagnosis?

Erosive and oozing lesions of the nipple, especially when unilateral, should raise suspicion about malignant neoplasms. Herein we report a patient with typical clinical and histopathological features of erosive adenomatosis of the nipple (EAN). It is an uncommon, benign proliferative process of lactiferous ducts of the nipple. Clinically, EAN is characterized by erosion, serous discharge, edema, itching, and erythema of one of the nipples. Complete excision of the tumor yields excellent results. Although EAN is a rare disease, clinicians must be aware of this benign neoplasm in patients with erosive lesions of the nipple. The main concern is the need to rule out malignant proliferations in the differential diagnosis. Histology is the gold standard for diagnosis. The coexistence of nipple adenoma and breast cancer is well-reported in the literature. Thus, it is necessary to encourage patients with a history of EAN to maintain regular breast screening.

Uncovering distinct progression patterns of tau deposition in progressive supranuclear palsy using [18F]Florzolotau PET imaging and subtype/stage inference algorithm.

BACKGROUND: Progressive supranuclear palsy (PSP) is a primary 4-repeat tauopathy with diverse clinical phenotypes. Previous post-mortem studies examined tau deposition sequences in PSP, but in vivo scrutiny is lacking. METHODS: We conducted [18F]Florzolotau tau positron emission tomography (PET) scans on 148 patients who were clinically diagnosed with PSP and 20 healthy controls. We employed the Subtype and Stage Inference (SuStaIn) algorithm to identify PSP subtype/stage and related tau patterns, comparing clinical features across subtypes and assessing PSP stage-clinical severity association. We also evaluated functional connectivity differences among subtypes through resting-state functional magnetic resonance imaging. FINDINGS: We identified two distinct subtypes of PSP: Subtype1 and Subtype2. Subtype1 typically exhibits a sequential progression of the disease, starting from subcortical and gradually moving to cortical regions. Conversely, Subtype2 is characterized by an early, simultaneous onset in both regions. Interestingly, once the disease is initiated, Subtype1 tends to spread more rapidly within each region compared to Subtype2. Individuals categorized as Subtype2 are generally older and exhibit less severe dysfunctions in areas such as cognition, bulbar, limb motor, and general motor functions compared to those with Subtype1. Moreover, they have a more favorable prognosis in terms of limb motor function. We found significant correlations between several clinical variables and the identified PSP SuStaIn stages. Furthermore, Subtype2 displayed a remarkable reduction in functional connectivity compared to Subtype1. INTERPRETATION: We present the evidence of distinct in vivo spatiotemporal tau trajectories in PSP. Our findings can contribute to precision medicine advancements for PSP. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (number 82272039, 81971641, 82021002, and 92249302); Swiss National Science Foundation (number 188350); the STI2030-Major Project of China (number 2022ZD0211600); the Clinical Research Plan of Shanghai Hospital Development Center of China (number SHDC2020CR1038B); and the National Key R&D Program of China (number 2022YFC2009902, 2022YFC2009900), the China Scholarship Council (number 202006100181); the Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198).

Improved interpretation of 18F-florzolotau PET in progressive supranuclear palsy using a normalization-free deep-learning classifier.

While 18F-florzolotau tau PET is an emerging biomarker for progressive supranuclear palsy (PSP), its interpretation has been hindered by a lack of consensus on visual reading and potential biases in conventional semi-quantitative analysis. As clinical manifestations and regions of elevated 18F-florzolotau binding are highly overlapping in PSP and the Parkinsonian type of multiple system atrophy (MSA-P), developing a reliable discriminative classifier for 18F-florzolotau PET is urgently needed. Herein, we developed a normalization-free deep-learning (NFDL) model for 18F-florzolotau PET, which achieved significantly higher accuracy for both PSP and MSA-P compared to semi-quantitative classifiers. Regions driving the NFDL classifier's decision were consistent with disease-specific topographies. NFDL-guided radiomic features correlated with clinical severity of PSP. This suggests that the NFDL model has the potential for early and accurate differentiation of atypical parkinsonism and that it can be applied in various scenarios due to not requiring subjective interpretation, MR-dependent, and reference-based preprocessing.

Thyroglossal Duct Cyst Carcinoma With Synchronous Thyroid Papillary Carcinoma: A Case Report and Literature Review.

Thyroglossal duct cysts (TGDC) are one of the most common congenital anomalies in the neck. Malignant transformation of these cysts is rare and synchronous involvement of the thyroid gland is even rarer. We report a case of synchronous occurrence of carcinoma in the thyroglossal duct cyst and thyroid gland and review the relevant literature. A 24-year-old woman who presented with a midline cervical mass, clinical examination, and complementary study was suggestive of a thyroglossal cyst with papillary carcinoma on fine-needle aspiration biopsy (FNAB) synchronous with thyroid papillary carcinoma with no cervical ganglion metastases documentation. Sistrunk's procedure plus total thyroidectomy was performed. With the clinical resemblance of benign and malignant cysts and the limitations of imaging techniques to distinguish between them, FNAB might be of use. Surgical treatment is warranted for the treatment of thyroglossal duct cyst carcinoma, but controversy still exists as to the extent of the surgical intervention. Sistrunk's procedure seems to be considered the gold standard when there is no evidence of thyroid involvement. However, in the presence of concomitant thyroid carcinoma, total thyroidectomy and cervical lymphadenectomy for evident node metastases are required. In the case of synchronous thyroglossal and thyroid carcinoma, most authors recommend pursuing both radioiodine therapy and hormone ablation. Thyroglossal duct cyst carcinoma is an uncommon feature that can arise from clusters of thyroid cells found within the cyst as in the present case. When confronted with this diagnosis it is fundamental to take into consideration the possibility of synchronous lesions as well as the extent of local and distance disease, since it has a direct influence on the choice of treatment provided to the patient. As there was a synchronous presence of papillary carcinoma in both the thyroglossal cyst and the thyroid gland, both the Sistrunk procedure and total thyroidectomy were performed, and radioiodine therapy was pursued as well as hormone ablation.

Porphyria Cutanea Tarda in a Patient with End-Stage Renal Disease: A Case of Successful Treatment with Deferoxamine and Ferric Carboxymaltose.

Porphyria cutanea tarda (PCT) is a rare disease, with a strong association with hepatitis C virus. PCT is particularly problematic in end-stage renal disease patients as they have no renal excretion of porphyrins and these are poorly dialyzed. Also, conventional treatment of PCT is compromised in these patients as hydroxychloroquine is contraindicated, phlebotomies with the stipulated frequency are poorly tolerated in already anaemia-prone patients, and iron-chelating agents are less efficient in removing iron and contribute to worsening anaemia. The authors report a patient on haemodialysis, with hepatitis C infection, that is diagnosed with PCT. Despite the good clinical results with deferoxamine, she became dependent on blood transfusions because of her ferropenic state. Every time oxide iron was started, the patient developed clinical features of the disease, resolving after the suspension of the drug. A decision was made to start the patient on ferric carboxymaltose, which was well tolerated without disease symptoms and need of further blood transfusions. This case suggests that deferoxamine is efficient in treatment of porphyria cutanea tarda. Also, ferric carboxymaltose may be a valuable option for refractory anaemia in patients with this disease and end-stage renal disease, as it seems to provide iron without clinical relapse of the disease.

[Syphilis: Prevalence in a Hospital in Lisbon]. / Sífilis: Prevalência num Hospital de Lisboa.

INTRODUCTION: Syphilis is a sexual and vertical transmitted disease. Its incidence is increasing in Europe, particularly, in Portugal. MATERIAL AND METHODS: A descriptive, retrospective study was performed based on positive treponemal tests from January to December 2013, at the Santa Maria Hospital, Lisbon. In-patients and out-patients evaluated in medical appointments and at the emergency department were included. We proceeded to epidemiological characterization, disease classification and definition of risk factors. RESULTS: We obtained a sample of 580 patients, of whom 51 with no clinical data and 45 with false positive serologies were excluded. There was a predominance of male patients (75%) and a mean age of 47 years. Most (59%) had syphilis successfully treated in the past and 3.7% were in follow-up. We recorded 13 primaries syphilis, 71 cases of secondary syphilis, 40 cases of early latent syphilis, 49 unknown duration syphilis and five cases of late latent syphilis. In the early syphilis group, 42% (n = 124) were HIV-positive and, in 8% both diagnosis were done simultaneously. DISCUSSION: We emphasize the high prevalence of syphilis/HIV co-infection in patients with early syphilis, reinforcing the importance of promoting the use of preventive measures. We obtained 11% of patients with late clinical forms, which are notifiable since June 2014, in Portugal. All serological tests for the diagnosis of syphilis have limitations which emphasizes the importance of clinical-laboratory correlation. CONCLUSION: Syphilis remains an important public health problem. It is necessary to establish education programs, screening and follow-up strategies to reduce their prevalence and to perform more efficient screening of the partners.

Introdução: A sífilis é uma doença de transmissão sexual e vertical. A sua incidência está a aumentar na Europa, particularmente em Portugal. Material e Métodos: Estudo retrospetivo baseado na análise laboratorial de testes treponémicos positivos, entre janeiro e dezembro de 2013, no Hospital de Santa Maria. Foram incluídos doentes internados, da consulta externa, do hospital dia e da urgência. Procedeu-se a caraterização epidemiológica, classificação da doença e de fatores de risco associados. Resultados: Obteve-se uma amostra de 484 doentes, após exclusão de 51 por ausência de dados clínicos nos processos e de 45 por valores falsos positivos. Verificou-se predomínio do sexo masculino (75%) e idade média de 47 anos. A maioria (59%) tinha testes serológicos compatíveis com sífilis no passado e 3,7% encontrava-se em vigilância clínica. Diagnosticou-se sífilis primária em 13doentes, secundária em 71, latente precoce em 40, latente indeterminada em 49 e latente tardia em cinco. No grupo sífilis recente, 42% (n = 124) eram seropositivos para o VIH e 8% tiveram, em simultâneo, este diagnóstico. Discussão: Salienta-se a elevada prevalência da coinfeção pelo VIH nos doentes com sífilis recente, reforçando a importância de promover a utilização de medidas preventivas. Registaram-se 11% de formas clínicas tardias, que são de notificação obrigatória desde junho de 2014. Todos os testes serológicos para o diagnóstico de sífilis apresentam limitações, o que enfatiza a importância da correlação clínico-laboratorial. Conclusão: A sífilis continua a ser um problema de saúde pública pelo que é necessário estabelecer programas de educação, rastreio e follow-up para reduzir a sua prevalência e tornar mais eficiente o rastreio dos parceiros.

Kaposi's sarcoma presenting as violaceous macules on the chest of a kidney transplanted patient.

Organ transplant recipients have a high incidence of cancer associated with persistent viral infections, such as human herpes virus 8. This virus is associated with Kaposi's sarcoma, and a change in the dose or type of immunosuppression regimen should be the first step in its treatment. A multidisciplinary approach with nephrologists, dermatologists and oncologists is necessary for the management of this disease. We report a clinical case with atypical presentation and discuss the treatment options.

Bullous hemorrhagic dermatosis induced by enoxaparin.

The bullous hemorrhagic dermatosis induced by enoxaparin is a rare adverse reaction, which may be under-reported given its favorable evolution. We report a 71-year-old man who developed hemorrhagic bullae at sites distant from subcutaneous enoxaparin injections. It is important that clinicians be aware of the different adverse reactions of these widely used drugs.

Bacillary angiomatosis in a HIV-positive patient with poor adherence to antiretroviral therapy.

Bacillary angiomatosis is a systemic disease caused by Bartonella (B.) henselae and B. quintana. Today it is a rare disease that occurs predominantly in patients with poor adherence to antiretroviral therapy or with late diagnosis of human immunodeficiency virus (HIV). We report on the case of a 40-year-old Caucasian female with HIV-1 and hepatitis B virus (HBV) co-infection diagnosed 17 years ago. She presented to the emergency department with an erythematous, painless nodule located on the left naso-genian fold. In the next few weeks the disease disseminated to the oral and left tarsal mucosa and to the palm of the left hand. The histopathological findings were suggestive of bacillary angiomatosis which was confirmed by polymerase chain reaction (PCR). The patient was treated with clarithromycin 500 mg bid per os for 3 months, with complete remission of the mucocutaneous lesions. Bacillary angiomatosis is a potentially fatal disease. Early diagnosis and treatment are critical in reducing the morbidity and mortality associated with it.

Cutaneous Alternariosis Caused by Alternaria infectoria: Three Cases in Kidney Transplant Patients.

The genus Alternaria has more than 80 species. Alternaria alternata and Alternaria infectoria are the most frequent species associated with infections in humans. Their clinical importance lies in the growing number of cases reported in immunocompromised patients. Herein, we report three cases of kidney-transplanted patients with different clinical presentations of cutaneous alternariosis and we discuss the treatment options.