Gut dysbiosis in cutaneous T-cell lymphoma is characterized by shifts in relative abundances of specific bacterial taxa and decreased diversity in more advanced disease.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) patients often suffer from recurrent skin infections and profound immune dysregulation in advanced disease. The gut microbiome has been recognized to influence cancers and cutaneous conditions; however, it has not yet been studied in CTCL. OBJECTIVES: To investigate the gut microbiome in patients with CTCL and in healthy controls. METHODS: A case-control study was conducted between January 2019 and November 2020 at Northwestern's busy multidisciplinary CTCL clinic (Chicago, Illinois, USA) utilizing 16S ribosomal RNA gene amplicon sequencing and bioinformatics analyses to characterize the microbiota present in fecal samples of CTCL patients (n = 38) and age-matched healthy controls (n = 13) from the same geographical region. RESULTS: Gut microbial α-diversity trended lower in patients with CTCL and was significantly lower in patients with advanced CTCL relative to controls (P = 0.015). No differences in ß-diversity were identified. Specific taxa were significantly reduced in patient samples; significance was determined using adjusted P-values (q-values) that accounted for a false discovery rate threshold of 0.05. Significantly reduced taxa in patient samples included the phylum Actinobacteria (q = 0.0002), classes Coriobacteriia (q = 0.002) and Actinobacteria (q = 0.03), order Coriobacteriales (q = 0.003), and genus Anaerotruncus (q = 0.01). The families Eggerthellaceae (q = 0.0007) and Lactobacillaceae (q = 0.02) were significantly reduced in patients with high skin disease burden. CONCLUSIONS: Gut dysbiosis can be seen in patients with CTCL compared to healthy controls and is pronounced in more advanced CTCL. The taxonomic shifts associated with CTCL are similar to those previously reported in atopic dermatitis and opposite those of psoriasis, suggesting microbial parallels to the immune profile and skin barrier differences between these conditions. These findings may suggest new microbial disease biomarkers and reveal a new angle for intervention.

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.

BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

Percutaneous radiofrequency ablation of renal tumors in high-risk patients: 10 years' experience. / Ablación percutánea mediante radiofrecuencia de tumores renales en pacientes de alto riesgo: 10 años de experiencia.

OBJECTIVE: To retrospectively evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) done to treat renal tumors in patients with high surgical risk or with the risk of developing multiple renal tumors in the medium term at our center over a period of 10 years. MATERIAL AND METHODS: Between 2005 and 2015, we used RFA to treat 89 T1a or T1b tumors in 87 patients (mean age, 73.7±10.87 years) with high surgical risk. We excluded patients treated with radiofrequency and embolization or microwave ablation. The tumors treated were clear cell carcinomas (43.6%), papillary renal carcinomas (17.2%), chromophobe renal cell carcinomas (10.3%), cystic tumors (2.2%), and an angiomyolipoma (1.1%). The mean size of the tumors was 2.6cm. Computed tomography and/or ultrasonography were used to guide the procedure. We analyzed the relation between the efficacy of the procedure and patients' age, the type of needle, the source of the patients, the size and location of the tumor, and the number of sessions required to achieve ablation. We recorded all complications. RESULTS: The RFA procedure was completed in all patients. The mean follow-up period was 32.1 months. The efficacy was 93.7%. A single session was sufficient in 87.5% of patients; 8% required two sessions and 4.5% required three sessions. The only factor associated with worse efficacy was the size of the tumor (p=0.03). The rate of complications was 5.6%. CONCLUSIONS: RFA is efficacious and safe, with results comparable to those reported in the literature.

γδ T-cell-rich variants of pityriasis lichenoides and lymphomatoid papulosis: benign cutaneous disorders to be distinguished from aggressive cutaneous γδ T-cell lymphomas.

BACKGROUND: T cells with a γδ phenotype have been associated with aggressive lymphomas. Yet, inflammatory skin disorders and low-grade lymphoproliferative disorders have rarely been described with a predominant γδ T-cell infiltrate. OBJECTIVES: To review our experience and determine the clinical relevance of the γδ T-cell phenotype in lymphomatoid papulosis (LyP) and pityriasis lichenoides (PL). METHODS: A retrospective dermatopathology file review looking for LyP and PL characterized by a γδ T-cell phenotype was performed. Clinical manifestations and course, histological features and molecular data were analyzed. RESULTS: Six of 16 cases of LyP and four of 23 cases diagnosed as PL during a 5-year period (2009-14) were identified. The median follow-up for the whole group was 16 months (range 3-64), showing an indolent clinical course in all cases. CONCLUSIONS: The detection of a predominantly γδ T-cell phenotype in papular lymphoid-rich infiltrates in the absence of other lesions is not associated with a clinically aggressive course. γδ T-cell-rich variants of LyP and PL may reflect a spectrum of related conditions. This is a single academic centre retrospective chart review of a relatively small sample.

Preoperative giant sacrococcygeal teratoma embolization in a newborn - A case report and a review. / Embolización preoperatoria de teratoma sacrococcigéo gigante en un recién nacido. Reporte de un caso y revisión.

Sacrococcygeal teratoma (SCT) is the most frequent congenital germ cell tumor. Patients have a higher risk of perinatal complications and death, with bleeding and cardiac decompensation being the most common causes of neonatal mortality. This is the case of a 35-week preterm newborn with a large SCT diagnosed at ultrasound screening in the second trimester. Preoperative selective embolization of the middle sacral artery and total surgical resection were performed postnatally with minimal blood loss. The patient was discharged at 25 days of life with a normal physical examination. Selective embolization prior to giant SCT resection is feasible and appears as a safe and useful technique in the control of perioperative bleeding.

El teratoma sacrococcígeo (TSC) es el tumor congénito de células germinales más frecuente. Los pacientes afectados tienen un mayor riesgo de complicaciones perinatales y muerte, siendo la hemorragia y la descompensación cardiaca las causas más comunes de mortalidad neonatal. Presentamos el caso de un recién nacido pretérmino de 35 semanas con un TSC de gran tamaño diagnosticado por ecografía en el segundo trimestre. La embolización selectiva preoperatoria de la arteria sacra media y la resección quirúrgica total postnatal se realizaron con una mínima pérdida de sangre. El paciente fue dado de alta a los 25 días de vida con un examen físico normal. La embolización selectiva antes de la cirugía de resección del TSC gigante es factible y aparece como una técnica segura y útil en el control del sangrado perioperatorio.

Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib.

BACKGROUND: This study examined clinicopathological findings and management of hand foot skin reaction (HFSR) to sorafenib and sunitinib in a dermatology referral center for cancer-related toxic effects. PATIENTS AND METHODS: We identified 12 patients who developed HFSR in a 1-year period (2007). Medical records and histological specimens were investigated for clinicopathological data and results on management. RESULTS: We identified 12 patients developing HFSR on treatment with sorafenib (83%) or sunitinib (17%). Majority presented with grade 3 (75%) HFSR and a median Skindex score of 43. Biopsies in seven patients showed horizontal layers of keratinocyte necrosis, which correlated to time of drug exposure: early (<30 days from initiation) leading to stratum granulosum-spinosum alterations and late (> or =30 days) resulting in stratum corneum pathology. Treatment with topical urea singly (n = 3), plus tazarotene (n = 7), or fluorouracil (n = 2) resulted in > or =2 grade improvement in the majority of patients (58%), with five patients (42%) improving one grade (P = 0.007). Median Skindex score at follow-up was 32 (P = 0.22). CONCLUSIONS: There are unique clinicopathological characteristics of HFSR due to the multikinase inhibitors that correlate with time of agent initiation. Treatment with topical agents having keratolytic, antiproliferative, and anti-inflammatory properties showed benefit.

Follicular mycosis fungoides: a histopathologic, immunohistochemical, and genotypic review.

Follicular mycosis fungoides (FMF) is a recognized variant of mycosis fungoides. In this review, the authors characterize the distinct histopathological and immunohistochemical patterns of FMF that have been reported in the literature. This article is an extensive review of the literature cited in Medline and own data of the authors. The major patterns of FMF histopathology, immunohistochemistry, and molecular genetics are summarized in this review. Histologically, the quintessential finding in FMF is small to medium atypical CD3+ CD4+ CD8- T lymphocytes around and within the epithelium of the hair follicles. This finding is requisite to the diagnosis. However, this finding may be obscured by a host of other patterns often identified in FMF. This includes basaloid folliculo-lymphoid hyperplasia, a granulomatous reaction, eosinophilic folliculitis, and follicular cystic changes with subtle atypical lymphocytes in the cyst wall. Follicular mucinosis (MF) and syringo-tropism are also variably present. Immunohistochemistry of all reported cases uniformly show a CD4+ T cell infiltrate. This review emphasizes and discusses the broad spectrum of histologic changes which may be seen in FMF, clues to the diagnosis, and some potential mimickers.

Interleukins in the treatment of mycosis fungoides.

Mycosis fungoides is typified by a cutaneous infiltrate of CD4+ lymphocytes with a Th2 phenotype. As the disease advances, there is increased expression of Th2 cytokines. This results in a subsequent suppression of Th1 cytokines and impaired cell mediated cytotoxic host response to the lymphoma cells. Disarming this cell mediate cytotoxic immune response creates a relentless cycle of disease progression. A cell mediated cytotoxic immune response can be stimulated with the use of Th1 cytokines such as IL-2 and IL-12. In this report, the Authors review the rational for the use of these particular cytokines in the treatment of mycosis fungoides. Further they comment on the experience and success regarding these two agents in phase I and II trials for the treatment of mycosis fungoides. Lastly, they discuss other potential cytokine therapies which could play a role in the future treatment of mycosis fungoides.

[The neuropsychological profile of mild cognitive impairment with involvement of multiple cognitive areas. The importance of amnesia in distinguishing two subtypes of patients]. / Perfil neuropsicológico del deterioro cognitivo leve con afectación de múltiples áreas cognitivas. Importancia de la amnesia en la distinción de dos subtipos de pacientes.

INTRODUCTION: The use of diagnostic criteria for mild cognitive impairment (MCI) that do not require the presence of amnesia enables patients to be classified into three types of MCI: pure amnestic MCI (aMCI), MCI with involvement of multiple cognitive functions and amnesia (mf-aMCI) and MCI with involvement of multiple cognitive functions without amnesia, or non-amnestic MCI (mf-nonaMCI). AIM: To determine whether patients with MCI with involvement of multiple functions (mfMCI) have a different profile of cognitive involvement depending on whether amnesia is present or not. PATIENTS AND METHODS: Out of a total sample of 175 patients with MCI, we studied 138 with mfMCI. Of these, 109 (79%) had memory disorders (mf-aMCI) and 29 (21%) did not (mf-nonaMCI). For each group of patients, we determined the percentage who scored below normal in each of the items on the abbreviated Barcelona test. RESULTS: Patients with mf-aMCI failed more frequently in temporal orientation, naming and semantic category evocation tests. Patients with mf-nonaMCI failed more often in motor praxis and abstraction tests. Differences were statistically significant. Additionally, it was noted that patients with mf-nonaMCI tended to make more mistakes in attention tests. CONCLUSIONS: The presence of amnesia allows us to identify an mf-aMCI group with a cognitive profile suggesting temporal involvement, unlike the mf-nonaMCI group, whose members have a cognitive profile that suggests subcortical compromise.

[Preventive treatment with topiramate enhances the quality of life of patients with migraine]. / El tratamiento preventivo con topiramato mejora la calidad de vida de los pacientes con migrana.

INTRODUCTION: Topiramate has recently proved to be safe and effective in the prevention of migraine and is currently the only neuromodulatory drug indicated for the prevention of migraine in Spain. AIM: To evaluate the adherence, effectiveness and safety of preventive treatment with topiramate in patients diagnosed with migraine. PATIENTS AND METHODS: A prospective, observational, multi-centre study was conducted in general neurology departments. Patients eligible for the study were those with migraine, above 14 years of age, who needed preventive treatment and in whom other preventive treatments had failed or for whom topiramate was believed to be the most suitable therapy as regards its profile of side effects. The effectiveness of the treatment, patient satisfaction, side effects and loss of body weight were all evaluated. Effectiveness of the treatment was evaluated by means of the reduction in the frequency of migraines and the score obtained on the Headache Impact Test (HIT-6). RESULTS: A total of 79 patients were evaluated. The dosage of topiramate ranged between 25 and 200 mg/day, with an average of 100 mg/day. 19% of the patients dropped out of the study due to side effects. Paresthesias were the most frequent reason for dropping out. No serious side effects were observed. 14% of the patients lost more than 5% of the base weight. The percentage of patients who responded was 58%. The degree of satisfaction of the patients who completed the follow-up was: good (80%), regular (11%) and poor (9%). CONCLUSIONS: Preventive treatment with topiramate significantly reduces the impact of migraine and the disability that results from it. Treatment is satisfactory and improves the quality of life in a large percentage of patients.

Primary cutaneous T-cell lymphoma: review and current concepts.

PURPOSE: Primary cutaneous T-cell lymphomas (CTCLs) encompass a wide variety of lymphomas that are characterized by the localization of the malignant lymphocytes to the skin at presentation. Advances in molecular biologic techniques, including immunophenotyping and gene rearrangement studies to determine clonality, have led to more frequent diagnosis of CTCL as well as more consistent subclassification of these entities. However, there continues to be confusion in the classification, prognosis, and management of patients with CTCL. The purpose of this review is to present a summary of the diagnosis, prognosis, and treatment of CTCL, with specific emphasis on mycosis fungoides (MF) and Sézary syndrome (SS). We also present a detailed discussion of the entities that make up the differential diagnosis of CTCL. DESIGN: We reviewed the medical literature on CTCL and other diseases that make up the differential diagnosis of CTCL. RESULTS AND CONCLUSION: MF and SS are the most common forms of CTCL. The etiology of this disease is still unknown. Patients may go for months to years with skin abnormalities before being diagnosed. MF/SS is an indolent disease and patients with T1 disease have a normal life expectancy. Patients who undergo transformation to large-cell lymphoma (8% to 23% of patients) have a poor prognosis, with mean survival ranging from 2 to 19 months. Treatment for MF/SS continues to be palliative. There are many new therapies that are currently being investigated in clinical trials, and the DAB(389)IL-2 fusion protein was recently approved for the treatment of refractory MF/SS.

Primary cutaneous B-cell lymphoma: review and current concepts.

PURPOSE: Primary cutaneous B-cell lymphoma (PCBCL) has only recently been recognized as a distinct clinical entity. With the advent of improved immunophenotyping and immunogenotyping, increasing numbers of PCBCL cases are being diagnosed. However, there is much confusion regarding the classification, treatment, and prognosis of these patients. The purpose of this article is to review and analyze the available data to provide the clinician with a concise summary of the diagnosis, prognosis, and treatment of PCBCL. DESIGN: We conducted a thorough review of the medical literature on PCBCL, with a focus on classification, prognosis, and treatment trials. RESULTS AND CONCLUSION: PCBCL is defined as a B-cell lymphoma originating in the skin. There is no evidence of extracutaneous disease at presentation and for 6 months after diagnosis, as assessed by adequate staging procedures. Currently, the European Organization for Research and Treatment of Cancer classification is the most concise disease classification scheme, dividing the subtypes of PCBCL by clinical behavior and histopathologic findings. Based on this classification, the most common subtype of PCBCL is follicular center cell lymphoma. PCBCL is generally an indolent form of lymphoma with a good prognosis. Although local cutaneous recurrences are observed in 25% to 68% of patients, dissemination to internal organs is rare. Five-year survival rates typically range from 89% to 96%. A specific subtype, large B-cell lymphoma of the leg, is noted to have a poorer prognosis, with a 5-year survival rate of 58%. Overly aggressive treatment of PCBCL has not been shown to improve survival or prevent relapse. The treatment of choice usually varies depending on the type of PCBCL, the body surface area, and the location of the involvement, as well as the age and general health condition of the patient. The majority of studies indicate that PCBCL is highly responsive to radiation therapy. Polychemotherapy should be reserved for involvement of noncontiguous anatomic sites or those with extracutaneous spread.

O6-alkylguanine-DNA alkyltransferase in cutaneous T-cell lymphoma: implications for treatment with alkylating agents.

Mycosis fungoides is a low-grade cutaneous T-cell lymphoma. Early treatment often involves the use of topical chemotherapy such as mechlorethamine or carmustine although single-agent oral chemotherapy with alkylators is common for advanced disease. Recently, in a Phase I study of the new alkylating agent temozolomide, two mycosis fungoides patients experienced a complete response. The mechanism of resistance to alkylating drugs such as temozolomide is thought to be due to the presence in tumor cells of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT). The protein mediates a reaction with the O6-position of guanine in DNA, removing the lesion and leaving guanine intact. We, therefore, examined the levels of AGT in CD4+ T lymphocytes obtained by negative antibody selection from the blood of noncancerous individuals and mycosis fungoides patients, and in paraffin-embedded sections from mycosis fungoides patch, plaque, or tumor lesions and cells from involved lymph nodes. AGT protein levels were measured by quantitative immunofluorescence microscopy using a monoclonal antibody against human AGT. Using this approach, the mean level of our positive control (AGT-expressing cells) was 84,807 molecules/nucleus; values below 5,000 molecules/nucleus are considered very low. The mean AGT level in CD4+ T lymphocytes from noncancerous and cancerous individuals was 18,618 (n = 12) and 8,593 (n = 5), respectively. The mean fraction of outliers in circulating CD4+ T lymphocytes from mycosis fungoides patients was statistically significantly lower than T cells in lymph nodes. AGT molecules/nucleus from lymph node biopsies from 8 of 10 patients showed low (< 10,000 molecules/nucleus) or undetectable levels (n = 5) of AGT. The mean AGT level from samples of mycosis fungoides patch/plaque and tumor was also low at 221 (n = 4) and 2,363 (n = 6), respectively. Surprisingly, Hut78, a mycosis fungoides T-cell lymphoma cell line, was positive for AGT activity (median: 77,700 molecules/nucleus), and Hut102--another mycosis fungoides cell line--was low (median: 5,990 molecules/nucleus). Because AGT is a primary means of cell resistance to alkylating agents, the low level of AGT in neoplastic T lymphocytes from patients with mycosis fungoides suggests that treatment with alkylating agents producing O6-alkylguanine adducts, such as carmustine or temozolomide, may produce improved clinical outcomes.

[Neuropathic pain as the reason for visiting Neurology: an analysis of its frequency]. / El dolor neuropático como motivo de consulta en Neurología: análisis de su frecuencia.

INTRODUCTION: Neuropathic pain (NP) is defined as pain that begins with or is caused by a primary injury or by a dysfunction in the nervous system. AIMS: Our aim was to evaluate how often patients visit Neurology as outpatients with NP as the main reason for referral. PATIENTS AND METHODS: A descriptive, cross sectional study was carried out on the use of the health care services; patients attended for the first time in a Neurology Screening visit were included consecutively. The variables studied were the following: the number of first visits and the total number of patients attended per visiting session, rate of patients with NP per visiting day, the topography and probable causation of the NP, and the rate of patients referred to the monographic NP clinic; the different quantitative variables are expressed in terms of their mean and standard deviation (SD), whereas the qualitative variables are given as their absolute value and the percentage. A total of 1,972 patients were attended, of whom 1,422 (72.1%) were first visits, with an average of 17.5 (SD: 2.5) new patients per visiting session. RESULTS: In all 113 patients clinically diagnosed with NP were identified, which represents a rate of 7.95% of the first visits. CONCLUSIONS: NP may be among the most frequent causes of the demand for neurological ambulatory care. The most common causes of NP were found to be trigeminal neuralgia, post-herpes neuralgia and diabetic polyneuropathy.

[An update on the diagnosis of vascular dementia]. / Actualización en el diagnóstico de la demencia vascular.

INTRODUCTION: Vascular dementia (VD) is the second most frequent cause of dementia after Alzheimer's disease in western societies. It includes a heterogeneous group of disorders in which vascular factors are believed to play a vital role in the development of cognitive impairment. Aims and development. Our aim was to determine what instruments can be used to diagnose VD and to what extent such a diagnosis is reliable. To this end, we review the diagnostic criteria that have been used up to now, the role played by neuropsychology, the value of neurosonology studies, and the growing development of neuroimaging techniques, especially magnetic resonance. CONCLUSIONS: Current diagnostic criteria for VD select a group that is clinically and aetiologically very heterogeneous. Such criteria need shifting towards new evidence-based criteria derived from analyses of population studies that focus on the early stages of the disease and that make a proper distinction between patients with mixed dementia. The subcortical subtype of vascular cognitive impairment (SVCI) is a form of vascular impairment that is more homogeneous and which selects more representative patients with a more predictable clinical pattern, natural history, response to treatment and prognosis. These characteristics make SVCI cases an ideal group for comparisons between clinical trials and studies.

Merkel cell carcinoma: a review.

Merkel cell carcinoma (MCC) is a rare aggressive primary cutaneous carcinoma with high mortality and rising incidence. The exact etiology of MCC remains unclear, but it is likely multifactorial with many factors playing a role, among these, ultraviolet radiation, immunosuppression, and recently, Merkel cell polyomavirus. Clinically MCC appears as an asymptomatic, firm, skin colored, sometimes reddish-blue, dome-shaped papule or plaque or subcutaneous nodule typically localized on the head and neck region that has grown rapidly. As its clinical presentation is generally non specific, the diagnosis relies on histological and immunohistochemical findings. Once diagnosis is established, adequate staging requires evaluation of regional and distant metastases. Treatment is based on multidisciplinary management although optimal therapy is controversial, at least in part due to a lack of quality data. Aggressive surgery frequently associated with adjuvant radiotherapy is used to improve the rates of locoregional recurrence and overall survival as well. Future targeted therapies may open new perspectives for the treatment of patients although high-quality, multicentre and randomized studies are needed. In this article, the current knowledge about MCC is reviewed and discussed.