Challenges in utilizing ALK expression to distinguish primary cutaneous from systemic anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a CD30+ peripheral T-cell lymphoma with a clinical spectrum including cutaneous and systemic presentations. While primary cutaneous ALCL (pcALCL) has a favorable prognosis, systemic ALCL (sALCL) has poorer survival outcomes. Expression of anaplastic lymphoma kinase (ALK) by malignant cells has been suggested to distinguish sALCL from pcALCL. However, there have been documented cases of ALK-positive ALCL confined to the skin. The present study reviewed characteristics of published cutaneous ALK-positive ALCL cases to distinguish between these two entities. In 23 identified adults with ALK-positive pcALCL, 26% developed systemic involvement and 74% had skin-limited disease. In 14 pediatric patients, 36% had both cutaneous and systemic involvement and 64% had cutaneous disease only. This analysis revealed that pcALCL and sALCL could not reliably be distinguished by ALK expression or nuclear vs. cytoplasmic localization. Localized treatment with frequent monitoring may be sufficient in ALK-positive pcALCL until there is evidence of progression. Physicians should be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK positivity and disease with skin recurrence.

Incidence of cutaneous melanoma and Merkel cell carcinoma in patients with primary cutaneous B-cell lymphomas: A population study of the SEER registry.

Introduction: The increased incidence of cutaneous melanoma (CM) and Merkel cell carcinoma (MCC) in patients with hematologic malignancies (HM) is well established. While the risk of CM has been assessed in some subtypes of HM including cutaneous T-cell lymphoma, the incidence in patients with primary cutaneous B-cell lymphoma (PCBCL) has not been interrogated. Methods: Here we evaluated the standardized incidence ratio (SIR) of CM and MCC in 5,179 PCBCL patients compared to approximately 1.5 billion individuals in the general population using the Surveillance, Epidemiology and End Results (SEER) database. Among patients with PCBCL, we identified subgroups that were at increased risk for CM or MCC as a second primary cancer. Results: We found 36 cases of CM in the PCBCL cohort (SIR, 1.35; 95% CI, 0.94-1.86), among which SIR was significantly elevated for non-Hispanic White patients compared to the general population (SIR, 1.48; 95% CI, 1.03-2.06). Males had a significantly increased risk of developing CM after a diagnosis of PCBCL (SIR, 1.60; 95% CI, 1.10-2.26). We found that males in the age group of 50-59 were at increased risk for CM development (SIR, 3.02; 95% CI, 1.11-6.58). Males were at increased risk of CM 1-5 years after PCBCL diagnosis (SIR, 2.06; 95% CI, 1.18-3.34). Patients were at greater risk of developing MCC within 1 year of diagnosis of PCBCL (SIR, 23.60; 95% CI, 2.86-85.27), particularly in patients who were over the age of 80 (SIR, 46.50; 95% CI, 5.63-167.96). Males aged 60-69 with PCBCL, subtype marginal zone, were also at increased risk for MCC (SIR, 42.71; 95% CI, 1.08-237.99). Conclusion: There is an increased incidence of CM in White, middle-aged males within 5 years of diagnosis of PCBCL and an increased risk of MCC in elderly patients within 1 year of PCBCL diagnosis. These data suggest that certain subgroups of patients with PCBCL may require more rigid surveillance for CM and MCC.

Immunosequencing applications in cutaneous T-cell lymphoma.

Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and disease monitoring in CTCL. The objective of this comprehensive review is to provide a thorough explanation of the application of immunosequencing in the context of CTCL. We describe the significance of T-cell clonality and the methods used to detect it, including a detailed comparison between PCR paired with capillary electrophoresis and HTS-TCR. The utilization of immunosequencing in the blood and skin of CTCL patients is discussed in depth, specifically outlining how HTS-TCR can assist in diagnosing CTCL, predicting outcomes, and tracking disease progression. Finally, we address the potential applications of immunosequencing in clinical management and research as well as the novel challenges it presents.

Utility of T-cell immunosequencing in distinguishing mycosis fungoides progression from treatment related cutaneous adverse events.

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a diagnosis of MF. After identification of the malignant TCR clone at baseline, immunosequencing can track the established malignant TCR sequence and its frequency over time with high sensitivity. As a result, immunosequencing clone tracking can aid in distinguishing disease progression from treatment side effects. Here, we present a case series to demonstrate how monitoring of the malignant T-cell frequency by immunosequencing can aid in diagnosis of mogamulizumab and mechlorethamine gel cutaneous adverse events.

Pulmonary vein isolation alone versus pulmonary vein isolation with additional extensive ablation for paroxysmal and persistent atrial fibrillation.

Background: The value of additional ablation beyond pulmonary vein isolation for atrial fibrillation (AF) ablation is unclear, especially for persistent AF. It is uncertain whether substrate modification with additional extensive ablation improves outcomes. We reviewed our experience to determine whether pulmonary vein isolation with additional extensive ablation (PVIEA) improves outcomes compared to pulmonary vein isolation alone (PVIA) for AF ablation. Methods: Consecutive cases of patients with PVIA versus PVIEA were compared between September 9, 2013 and December 12, 2020. Procedural data collected include radiofrequency ablation delivery time (RADT) and arrhythmia inducibility. Clinical data collected include sinus rhythm maintenance post-procedure. Results: A total of 235 patients were studied (67 PVIA and 168 PVIEA). RADT was shorter when comparing ablation with PVIA versus PVIEA (32 vs. 40 min; p = .04). More arrhythmias were inducible with PVIEA (p < .01). There was no difference in sinus rhythm maintenance by Kaplan-Meier survival analysis (log-rank test p = .75), after 3 or 12 months between groups overall, and when stratified by AF type (paroxysmal and persistent), left atrial volume, CHA2DS2-VASc score, left ventricular ejection fraction, or catheter ablation setting (high-power short-duration, standard-power standard-duration, temperature-controlled non-contact-force). Conclusion: AF ablation with PVIA or PVIEA produces similar sinus rhythm maintenance overall and when stratified by catheter setting and AF type. PVIA reduced procedure times and less arrhythmias were inducible post-ablation.

Recalcitrant Subcutaneous Panniculitis-Like T-Cell Lymphoma Responsive to Histone Deacetylase Inhibitor.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous T-cell lymphoma that usually presents with tender subcutaneous nodules on the trunk and extremities. Immunosuppressive therapy is considered first-line treatment for SPTCL, while multiagent chemotherapy is used for SPTCL complicated by hemophagocytic lymphohistiocytosis (HLH). Here, we report a 42-year-old Hispanic man that presented with a 5-year history of recurrent painful subcutaneous lesions in the absence of constitutional symptoms, lymphadenopathy, and hepatosplenomegaly. A punch biopsy revealed an atypical lymphoid infiltrate in between subcutaneous adipose lobules. Lymphocytes expressed CD3, CD8, and Beta F-1 and did not express CD4 and CD56. Based on clinical and histologic findings, the patient was diagnosed with SPTCL. In addition, laboratory findings did not demonstrate any evidence of HLH. He was initially started on both prednisone and hydroxychloroquine with no improvement. A trial of cyclosporine and methotrexate yielded no clinical improvement. As the lesions failed to resolve after treatment with multiple immunosuppressive agents, romidepsin, an intravenous histone deacetylase (HDAC) inhibitor, was initiated. After two cycles of romidepsin, the patient achieved complete clinical response. He continues to be in remission 12 months later with monthly maintenance therapy. This case illustrates that romidepsin can be useful as monotherapy for refractory SPTCL without HLH.

Endovascular Management of Complex Fenestration-Associated Aneurysms: A Single-Institution Retrospective Study and Review of Existing Techniques.

BACKGROUND: Aneurysms associated with fenestrations of intracranial arteries are exceptionally rare findings. Management strategies for these aneurysms are not well-defined, especially regarding endovascular treatment. We sought to investigate the strategies and feasibility of endovascular treatment approaches for various fenestration-associated intracranial aneurysms. METHODS: We performed a retrospective chart review of 2000 aneurysms treated endovascularly, identifying 8 aneurysms located at arterial fenestrations. The technical details and procedural outcomes were reviewed to identify common management approaches, technical nuances, and treatment outcomes. RESULTS: There were 3 (37.5%) aneurysms associated with fenestrations of the basilar artery or vertebrobasilar junction. All 3 were successfully treated with a previously undescribed coil-assisted flow-diversion technique, resulting in complete obliteration. Three (37.5%) aneurysms were associated with fenestrations of the anterior communicating artery. Of those, 2 were successfully treated with stent-assisted coil embolization and 1 with coil embolization alone. One (12.5%) aneurysm was associated with a fenestration of the paraclinoid internal carotid artery and 1 (12.5%) aneurysm found was at the takeoff of the posterior inferior cerebellar artery at a fenestration of the vertebral artery. Both were successfully treated with coil-assisted flow diversion. There were no permanent procedural complications. Major considerations for endovascular management of these aneurysms were the dominance of fenestration trunks, aneurysms arising from the fenestration apex or a fenestration limb, amenability to flow diversion, and anticipation of vascular remodeling. CONCLUSIONS: Fenestration-associated aneurysms are very rare. We have identified common factors to help guide decision-making for endovascular approaches and demonstrate successful aneurysm treatment using these methods.

Incidence and predictors of ophthalmic artery occlusion in intra-arterial chemotherapy for retinoblastoma.

BACKGROUND: Retinoblastoma is the most common primary intraocular malignancy in children. OBJECTIVE: To determine the incidence of ophthalmic artery (OA) occlusion in patients treated with selective ophthalmic artery catheterization (OAC) for chemotherapy infusion for retinoblastoma. Also, to evaluate technical, anatomical, tumorous, and patient-related factors that are predictors of OA occlusion. METHODS: A retrospective chart review was performed for patients diagnosed with intraocular retinoblastoma and managed with intra-arterial chemotherapy (IAC). RESULTS: The total study cohort included 208 retinoblastoma tumors of 208 eyes in 197 consecutive patients who underwent 688 attempted IAC infusions overall with a total of 624 successful OAC infusions. The total incidence of ophthalmic artery thrombosis was 11.1% (23/208). The numbers of successful OAC procedures before diagnosing OA occlusion were one OAC in six cases (27.3%), two in seven cases (31.8%), three in four cases (18.2%), four in one case (4.5%), five in two cases (9.1%), and six in one case (4.5%). CONCLUSIONS: Local factors relating to the chemotherapy and selective microcatheterization of the OA are essential factors in the development of OA thrombosis, as seen by the association of OA thrombosis with the frequency of IAC.

Transradial approach for diagnostic cerebral angiograms in the elderly: a comparative observational study.

BACKGROUND: The transradial approach (TRA) reduces mortality, morbidity, access site complications, hospital cost, and length of stay while maximizing patient satisfaction. We aimed to assess the technical success and safety of TRA for elderly patients (aged ≥75 years). METHODS: A retrospective chart review and comparative analysis was performed for elderly patients undergoing a diagnostic cerebral angiogram performed via TRA versus transfemoral approach (TFA). Also, a second comparative analysis was performed among the TRA cohort between elderly patients and their younger counterparts. RESULTS: Comparative analysis in the elderly (TRA vs TFA) showed no significant differences for contrast dose per vessel (43.7 vs 34.6 mL, P=0.106), fluoroscopy time per vessel (5.7 vs 5.2 min, P=0.849), procedure duration (59.8 vs 65.2 min, P=0.057), conversion rate (5.8% vs 2.9%, P=0.650), and access site complications (2.3% vs 2.9%, P=1.00). Radiation exposure per vessel (18.9 vs 51.9 Gy cm2, P=0.001) was significantly lower in the elderly TRA group.The second comparison (TRA in elderly vs TRA in the young) showed no significant differences for contrast dose per vessel (43.7 vs 37.8 mL, P=0.185), radiation exposure per vessel (18.9 vs 16.5 Gy cm2, P=0.507), procedure duration (59.8 vs 58.3 min, P=0.788), access site complication (2.3% vs 1.7%, P=0.55), and conversation rate (5.8% vs 1.8%, P=0.092). A trend for prolonged fluoroscopy time per vessel (5.7 vs 4.7 min, P=0.050) was observed in the elderly TRA group. CONCLUSIONS: TRA is a technically feasible and safe option for diagnostic neurointerventional procedures in the elderly. Our small elderly cohort was not powered enough to show a significant difference in terms of access site complications between TRA and TFA.

Carotid Blowout Management in the Endovascular Era.

BACKGROUND: Carotid blowout syndrome (CBS) is a potential complication of head and neck cancer, and its therapy is associated with high morbidity and mortality. Recent advances in endovascular techniques have improved patient outcomes. In this study, we report outcomes of emergent endovascular intervention for CBS. METHODS: We conducted a retrospective analysis of a prospectively maintained neurovascular database and identified 38 consecutive endovascular procedures for CBS from 2008-2019 at our institution. Data collection was performed on patient demographics, type of cancer, previous cancer treatments, type of CBS, location of bleed, diagnostic workup, endovascular treatment, and procedural outcomes and complications. RESULTS: A total of 38 consecutive endovascular procedures for CBS were performed from 2008-2019 at our single academic institution. Technical success was achieved in 100% of endovascular procedures. Procedural stroke occurred in 1 (2.6%) procedure, procedural mortality occurred in 1 (2.6%) procedure, recurrent CBS occurred in 4 (10.5%) procedures, and fatal rehemorrhage occurred in 1 (2.6%) procedure. Regarding secondary outcomes, delayed stroke/transient ischemic attack occurred in 1 (2.6%) procedure, whereas there were no cases of delayed infectious complications. CONCLUSIONS: The endovascular treatment of CBS is safe and effective with relatively low rates of morbidity and mortality compared with other currently available treatment modalities. However, the overall rate of complications demands attention and sheds light on the need for further improvement in management.

Coil Embolization of Wide-Neck Bifurcation Aneurysms via Shouldering and Framing: A Safe Alternative to Conventional Techniques.

OBJECTIVE: Double stent-assisted coiling of wide-neck bifurcation aneurysms (WNBAs) can be technically challenging with high thromboembolic rates. Single stent-assisted coiling (SSAC) decreases procedural complexity and thromboembolic risk but increases risk of coil prolapse and recanalization. In this study, we present our institution's experience with SSAC of WNBA performed via a "shouldering" and "framing" with a single Atlas stent and a spherical 3-dimensional (3D) Stryker coil. METHODS: A retrospective review of 35 patients who underwent SSAC of WNBA performed via a shouldering and framing with a single Atlas stent and a spherical 3D Stryker coil from 2018 to 2019. Data collection were performed on baseline demographics, clinical presentation, aneurysm characteristics, angiographic and functional outcomes, and perioperative and postoperative complications. RESULTS: Of 35 patients, the mean age was 59.9 ± 11.6 years and 25/35 (71.4%) were women. The mean aneurysm diameter was 6.3 ± 3.4 mm, the mean neck size was 3.9 ± 1.3 mm, and the mean dome-to-neck ratio was 1.5 ± 0.6. Initial complete/near-complete occlusion was demonstrated in 30/35 (85.7%) patients. On angiographic follow-up at a mean of 6 months, 9/24 (37.5%) patients showed progressive thrombosis, 13/24 (54.2%) showed stable occlusion, and 2/24 (8.5) showed recanalization. Thromboembolic events occurred in 2/35 (5.7%) patients, intraoperative technical complications occurred in 2/35 (5.7%) patients, and access-site complications occurred in 2/35 (5.7%) patients. The were no cases of retreatment, rehemorrhage, or procedural-related permanent morbidity or mortality. CONCLUSIONS: Coil embolization performed via shouldering with a single Atlas stent and framing with a spherical 3D Stryker coil is a feasible, safe, and effective neuroendovascular treatment for WNBAs.

HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4(+) T cell increases in antiretroviral-treated South African volunteers: a randomized phase II clinical trial.

BACKGROUND: Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. METHODS: The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 µg) given intradermally, three times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4(+) T-cell counts ≥200 cells/µL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4(+) T-cell counts and therapy compliance. RESULTS: Immunization was safe and well-tolerated and induced durable, high titers anti-Tat B-clade antibodies in 97 % vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade envelope in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4(+) T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4(+) T-cell numbers over study entry levels as compared to placebo. CONCLUSIONS: The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. Trial registration ClinicalTrials.gov NCT01513135, 01/23/2012.

Factors associated with development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics.

This study investigated the association between presence of respiratory pathogens and development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics. In total, 86 dogs were tested using a commercial PCR respiratory panel; 64 dogs were considered as cases and 22 were control dogs matched by veterinary clinic. No control animals (0/22) were positive for canine parainfluenza virus (CPIV), whereas 27/64 (42%) CIRDC cases were positive. Furthermore, 81% of case dogs tested positive for Mycoplasma cynos, compared with 73% of control dogs. Canine respiratory corona virus (CRCoV) was detected in no control dogs compared with 9.4% of clinical dogs. No animals were positive for any influenza virus type A present in the diagnostic panel. Presence of CPIV was associated (P < 0.01) with the occurrence of CIRDC after adjustment for demographic factors and presence of CRCoV (P = 0.09).

Facteurs associés au développement de l'ensemble des maladies respiratoires infectieuses canines (MRIC) chez les chiens dans 5 cliniques pour petits animaux au Canada. Cette étude a étudié l'association entre la présence d'agents pathogènes et le développement de l'ensemble des maladies respiratoires infectieuses canines (MRIC) chez les chiens dans cinq cliniques pour petits animaux au Canada. Au total, 86 chiens ont été testés à l'aide d'un panel respiratoire commercial d'ACP; 64 chiens ont été considérés comme des cas et 22 étaient des chiens témoins jumelés par la clinique vétérinaire. Aucun animal témoin (0/22) n'était positif pour le virus parainfluenza canin (VPIC), tandis que 27/64 (42 %) des cas de MRIC étaient positifs. De plus, 81 % des chiens des cas ont eu un résultat positif pour Mycoplasma cynos, comparativement à 73 % des chiens témoins. Le coronavirus respiratoire canin (COVRC) n'a pas été détecté chez aucun chien, comparativement à 9,4 % des chiens cliniques. Aucun animal n'a eu un résultat positif pour tous les types du virus de l'influenza de type A dans le groupe de diagnostic. La présence du VPIC était associée (P < 0,01) à l'occurrence d'une MRIC après l'ajustement des facteurs démographiques et de la présence du COVRC (P = 0,09).(Traduit par Isabelle Vallières).

Prevalence of methicillin-resistant staphylococci in canine pyoderma cases in primary care veterinary practices in Canada: A preliminary study.

Pyoderma in dogs is most commonly caused by Staphylococcus spp., and significant emergence of methicillin resistance in staphylococcal pyoderma has been reported. This preliminary study of the prevalence of methicillin resistance in canine pyoderma cases in Canadian primary care veterinary practices revealed that methicillin-resistant Staphylococcus spp. were present in 12.1% of 149 staphylococcal positive skin culture cases.

Prévalence des staphylocoques résistants à la méthicilline dans les cas de pyodermites canines dans les pratiques vétérinaires de soins primaires au Canada : une étude préliminaire. La pyodermite chez les chiens est le plus communément causée par Staphylococcus spp. et on a signalé une émergence importante de la résistance à la méthicilline pour les pyodermites staphylococciques. Cette étude préliminaire de la prévalence de la résistance à la méthicilline pour les cas de pyodermites canines dans les pratiques vétérinaires de soins primaires au Canada a révélé que des Staphylococcus spp. résistants à la méthicilline étaient présents dans 12,1 % des 149 cas de cultures de la peau positives pour les staphylocoques.(Traduit par Isabelle Vallières).

Raw food diets in companion animals: a critical review.

Feeding of raw meat-based diets to pets has become an increasingly popular trend amongst pet owners. Owners, who desire to provide the best for their pets, seek veterinary opinions about food options. This paper reviews and applies standards of evidence-based medicine to grade the available scientific literature that addresses the nutritional benefits or risks, infectious disease risks, and public health implications of raw, meat-based pet diets. Although there is a lack of large cohort studies to evaluate risk or benefit of raw meat diets fed to pets, there is enough evidence to compel veterinarians to discuss human health implications of these diets with owners.

The prevalence of intestinal parasites in dogs and cats in Calgary, Alberta.

The prevalence of endoparasites was evaluated in 619 dogs and 153 cats in the Calgary, Alberta region. Both homed and shelter-sourced pets were evaluated, and prevalence was assessed in various age groups. The overall endoparasite prevalence was 16.5% in canine samples and 7.2% in feline samples. The most common intestinal parasites in dogs were Giardia (8.1%) and ascarids (4.2%). The most common feline endoparasite was ascarids (6.5%). This study will help veterinarians to better plan diagnostic and preventative strategies with regard to companion animal intestinal parasites.