Anaplastic Large-Cell Lymphoma (ALCL) First Manifested as a Rapidly Progressive Acute Respiratory Failure (RF): Lymph Node Biopsy Negative Presentation Posing a Diagnostic Challenge.

Anaplastic large-cell lymphoma (ALCL) is an aggressive subtype of non-Hodgkin lymphoma. There are two forms of ALCL: primary and secondary. Primary can be systemic, affecting multiple organs, or cutaneous, affecting mainly the skin. A secondary form occurs when another lymphoma undergoes an anaplastic transformation. ALCL rarely presents as initial symptoms of respiratory failure. In most of these situations, the trachea or bronchial involved with an obstruction was present. We present an unusual case of ALCL where the patient rapidly progressed to acute hypoxic respiratory failure with a patent bronchus and trachea. Unfortunately, the patient rapidly deteriorated and died before diagnosis. Only upon at autopsy, it was found that his lung parenchyma was diffusely involved with ALCL. The autopsy report showed that the patient had CD-30 anaplastic lymphoma kinase (ALK)-negative ALCL diffusely involving all lung fields.

Prolonged persistence of HIV-infected cells in tissues after allogeneic hematopoietic transplant

Background: HIV persistence during antiretroviral therapy (ART), prevents HIV eradication or control. Mechanisms responsible for HIV persistence, including in tissues, are not well understood. Here we investigated persistence of HIV-infected cells in tissues for >200 days in an individual who had successful allogeneic hematopoietic cell transplant (Allo-HCT;donor CCR5 wild-type) but developed acute lymphocytic interstitial pneumonia after COVID vaccination and expired. Method(s): Clinical and autopsy records were reviewed. HIV in tissue samples and mononuclear cells (prepared by ficoll from lung and spleen) were studied by single genome sequencing (SGS, 1.1 kb gag) and single-copy PCR for HIV DNA. Result(s): Study participant was a 38 yo man with HIV/AIDS on ART with HIV RNA<50 c/ml for >3 years who had reducedintensity conditioning, HLA-mismatched unrelated donor allo-HCT for primary refractory ALK-negative anaplastic large cell lymphoma. His course was remarkably uncomplicated:100% engraftment of donor CD3 and myeloid subsets confirmed by day +42 post-HCT;100% donor cells (CD4, CD8, CD19, CD14, CD56) confirmed by day +100. Per protocol, he was off all immunosuppression on day +60, did not develop acute graft-versus-host disease (GVHD), and maintained ART with HIV RNA<20 c/ml. Immune reconstitution was robust: NK, CD8, and B cells within normal range, CD4=172 cells/muL at d+100. He received SARS-CoV2 mRNAvaccine (Moderna) on days +107 and +144. On d+155, he developed dyspnea, hypoxia with acute lymphocytic interstitial pneumonia, presumed vaccinerelated, with no signs of GVHD, pulmonary infection, or lymphoma. HIV-1 RNA remained <20 except 21 c/ml noted shortly before expiring on d+207. Postmortem notable only for diffuse alveolar damage with fibrosis and a small white pulpdepleted spleen. Single copy assay detected HIV DNA in brain (thalamus, frontal lobe, midbrain), lymph node, and jejunum (1.6-16 copies/106 tissue cells) but not liver, spleen, or affected lung (<0.2 copies/106 cells). SGS revealed HIV sequences were non-identical, demonstrating multiple distinct populations of infected cells were present. Conclusion(s): HIV populations are diverse in tissues even after extensive lymphodepleting chemotherapy and allo-HCT. Complete donor engraftment in tissues, including brain, may take significantly longer than engraftment measured in peripheral blood. Eradication strategies will require evaluation of tissue compartments. Copyright © 2022 Elsevier Ltd

Inhibitors of Activin Receptor-like Kinase 5 Interfere with SARS-CoV-2 S-Protein Processing and Spike-Mediated Cell Fusion via Attenuation of Furin Expression.

Screening of a protein kinase inhibitor library identified SB431542, targeting activin receptor-like kinase 5 (ALK5), as a compound interfering with SARS-CoV-2 replication. Since ALK5 is implicated in transforming growth factor ß (TGF-ß) signaling and regulation of the cellular endoprotease furin, we pursued this research to clarify the role of this protein kinase for SARS-CoV-2 infection. We show that TGF-ß1 induces the expression of furin in a broad spectrum of cells including Huh-7 and Calu-3 that are permissive for SARS-CoV-2. The inhibition of ALK5 by incubation with SB431542 revealed a dose-dependent downregulation of both basal and TGF-ß1 induced furin expression. Furthermore, we demonstrate that the ALK5 inhibitors SB431542 and Vactosertib negatively affect the proteolytic processing of the SARS-CoV-2 Spike protein and significantly reduce spike-mediated cell-cell fusion. This correlated with an inhibitory effect of ALK5 inhibition on the production of infectious SARS-CoV-2. Altogether, our study shows that interference with ALK5 signaling attenuates SARS-CoV-2 infectivity and cell-cell spread via downregulation of furin which is most pronounced upon TGF-ß stimulation. Since a TGF-ß dominated cytokine storm is a hallmark of severe COVID-19, ALK5 inhibitors undergoing clinical trials might represent a potential therapy option for COVID-19.

Target Specific Inhibition of Protein Tyrosine Kinase in Conjunction With Cancer and SARS-COV-2 by Olive Nutraceuticals.

The fact that viruses cause human cancer dates back to the early 1980s. By reprogramming cellular signaling pathways, viruses encoded protein that can regulate altered control of cell cycle events. Viruses can interact with a superfamily of membrane bound protein, receptor tyrosine kinase to modulate their activity in order to increase virus entrance into cells and promotion of viral replication within the host. Therefore, our study aimed at screening of inhibitors of tyrosine kinase using natural compounds from olive. Protein tyrosine kinase (PTK) is an important factor for cancer progression and can be linked to coronavirus. It is evident that over expression of Protein tyrosine kinase (PTK) enhance viral endocytosis and proliferation and the use of tyrosine kinase inhibitors reduced the period of infection period. Functional network studies were carried out using two major PTKs viz. Anaplastic lymphoma kinase (ALK) and B-lymphocytic kinase (BTK). They are associated with coronavirus in regulation of cell signaling proteins for cellular processes. We virtually screened for 161 library of natural compounds from olive found overexpressed in ALK and BTK in metastatic as well as virus host cells. We have employed both ligand and target-based approach for drug designing by high throughput screening using Multilinear regression model based QSAR and docking. The QSAR based virtual screening of 161 olive nutraceutical compounds has successfully identified certain new hit; Wedelosin, in which, the descriptor rsa (ratio of molecular surface area to the solvent accessible surface area) plays crucial role in deciding Wedelosin's inhibitory potency. The best-docked olive nutraceuticals further investigated for the stability and effectivity of the BTK and ALK during in 150 ns molecular dynamics and simulation. Post simulation analysis and binding energy estimation in MMGBSA further revealed the intensive potential of the olive nutraceuticals in PTK inhibition. This study is therefore expected to widen the use of nutraceuticals from olive in cancer as well as SARS-CoV2 alternative therapy.

Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone (Chep-BV) followed by bv consolidation in patients with cd30-expressing peripheral tcell lymphomas

Introduction: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphomas associated with poor outcomes following anthracycline-based chemotherapy, even when consolidative autologous stem cell transplantation (ASCT) is used. CD30 expression is universal in anaplastic large cell lymphoma (ALCL) and is frequently expressed in other PTCL subtypes. Brentuximab vedotin (BV) is a CD30-directed antibody drug conjugate that prolongs progression-free survival (PFS) and overall survival (OS) when combined with cyclophosphamide, doxorubicin, and prednisone (CHP) as compared to CHOP chemotherapy (Horwitz, 2020). Although a majority of pts treated with BV-CHP remained in durable remission (5y PFS 51%), there is room for improvement. Based on retrospective studies that demonstrated improved outcomes in younger pts, the addition of etoposide to CHOP (CHOEP) is commonly used as initial therapy for PTCL. We performed a multicenter phase 2 trial to evaluate the safety and efficacy of adding etoposide to BV-CHP (CHEP-BV) followed by BV consolidation in pts with newly diagnosed CD30-expressing PTCL. Methods: Adults with newly diagnosed CD30+ (≥ 1% of tumor cells by local pathology) PTCL were eligible, including pts with ALK+ ALCL and IPI score ≥ 2, ALK-negative ALCL, PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), adult Tcell leukemia/lymphoma (ATLL), among others. After accrual of 28 pts, the protocol was amended to allow enrollment of 20 additional pts with CD30+ non-ALCL PTCL (with ALCL allowed in Canada). Pts could receive prephase steroids and/or 1 cycle of CHOPequivalent chemotherapy prior to study entry. 6 pts were treated in a safety lead-in cohort and all pts received CHEP-BV at the recommended phase 2 dose: 6 x 21-day cycles of CHP+BV (1.8mg/kg) on d1 and etoposide 100mg/m2 on d1-3. G-CSF prophylaxis was mandatory. Pts in response after CHEP-BV could receive BV consolidation (1.8mg/kg q3w) for up to 10 additional cycles (16 total BV cycles) either after ASCT or CHEP-BV if no ASCT was performed. The co-primary endpoints were safety and the CR rate (Deauville score 1-3) by PET-CT after CHEP-BV assessed by investigators according to the 2014 Lugano classification. Secondary endpoints were PFS and OS. Results: Accrual has completed and 48 pts were enrolled;all were evaluable for toxicity, 46 were evaluable for efficacy. 16 pts had ALCL (13 ALK+, 3 ALK-) and 32 had non-ALCL PTCL subtypes, including 18 with AITL, 11 with PTCL NOS, 2 with T-follicular helper PTCL, and 1 with ATLL. Baseline characteristics are shown in Table. 43 pts completed CHEP-BV, 2 had progressive disease (PD) prior to completion, 1 pt discontinued CHEP-BV early (MD discretion), 1 pt died due to COVID-19, and 1 remains on CHEP-BV. Of 43 pts who completed CHEP-BV, 24 proceeded to ASCT and 19 did not. 33 (74%) pts received BV consolidation (20 after ASCT, 13 directly after CHEP-BV) and completed a median 8 of the planned 10 cycles (range, 1-10). 13 pts completed all cycles of consolidation;19 pts discontinued early-12 due to adverse events (AE), 5 due to PD, and 2 due to patient/physician choice. The most frequent CHEP-BV related AEs (all grades, G) include fatigue (73%), peripheral sensory neuropathy (67%), anemia (62.5%), nausea (56%), neutropenia (50%), lymphopenia (44%), leukopenia (42%), thrombocytopenia (40%), elevated transaminases (33%). The most common G3+ AEs were neutropenia (37.5%), febrile neutropenia (23%), lymphopenia (21%), anemia (19%), thrombocytopenia (19%). There were 5 deaths, 4 due to PD and 1 due to COVID-19 infection during C3 of CHEP-BV. The interim (n=46) ORR and CR rates (after 3 CHEP-BV cycles, except 1 pt after 2) were 96% and 59% (27 CR, 17 PR), respectively. At completion of CHEP-BV (n=46), the ORR was 91% with 80% CR (37 CR, 5 PR, 4 PD). The ORR/CR rates in ALCL (n=16) vs non-ALCL (n=30) pts were 94%/94% vs 90%/73%, respectively. The ORR/CR rates in pts with CD30 expression 1-9% (n=15) vs 10+% (n=31) were 93%/67% and 90%/87%, respectively. The median follow-up in surviving pts is 1 .1 months (range, 0.9-32.5). The overall 18mo PFS and OS were 61% and 89%;18mo PFS by subgroup: ALCL 81%, non-ALCL 49%, CD30 1-9% 48%, CD30 10+% 67%. Landmark 1y PFS from end of CHEP-BV in responding pts (n=41) was 82% in pts who underwent ASCT vs 48% in pts who did not Conclusions: In a cohort of pts with mostly non-ALCL CD30-expressing PTCL, CHEP-BV (+/-ASCT) followed by BV consolidation was tolerable and effective.

Understanding and Targeting Pulmonary Arteriovenous Malformations Using Repurposed Drugs

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by multiple arteriovenous malformations(AVMs) which are direct connections between arteries and veins, bypassing the capillary bed. Severe epistaxis (nosebleeds) is the most common symptom, yet visceral AVMs in the brain (1-10%), lung (15-45%), liver and gastrointestinal tract cause significant morbidity and mortality due to embolic stroke, cerebral abscess, migraines, hemorrhagic stroke, seizures and life-threatening bleeding complications. In order to reduce the morbidity and mortality associated with HHT, we need a better understanding of HHT development and novel treatment approaches. Our aims are: Aim 1: To understand the cellular and molecular mechanisms of PAVM development in mice and to identify the cell behaviors and populations that give rise to PAVMs. Aim 2: To identify and target pathological downstream signaling in endothelial cells derived from iPSCs (iPSC-ECs)from HHT patients with visceral AVMs. Aim 3: To target pathological downstream signaling with repurposed drugs to prevent and reverse PAVMs in the mouse model. The short-term impact will be a better understanding of how AVMs form in the lung and potentially in other organs. The long-term impact will be the identification of potential novel treatments for AVMs.

Anaplastic large cell lymphoma presenting as hemophagocytic lymphohistiocytosis

INTRODUCTION: HLH is a rare syndrome with an incidence of 1.2 cases per 1,000,000 individuals per year. Diagnosis of HLH is challenging given its varied presentation and strict diagnostic criteria. DESCRIPTION: A 40 year-old female with no medical history presented with two weeks of shortness of breath and cervical lymphadenopathy. She was evaluated in the ED on two separate occasions with workup significant for CT chest findings of mediastinal and axillary lymphadenopathy, pulmonary nodules and a left pleural effusion. Within one week, she presented a third time with worsening shortness of breath, fatigue and fevers. She was febrile, tachycardic, hypoxemic, leukopenic and thrombocytopenic. A repeat CT chest revealed increased lymphadenopathy and pleural effusion. She was started on empiric broad spectrum antibiotics and admitted to the hospital. Infectious workup, pleural fluid cytology and peripheral blood flow cytometry were negative. Bone marrow biopsy had markedly increased histiocytes and hemophagocytosis, but no evidence of malignancy. She developed progressive hypoxemia requiring intubation, shock requiring vasopressors and multiorgan failure. Fevers persisted with worsening pancytopenia, DIC, and markedly elevated inflammatory markers, notably a ferritin >33000. Further workup revealed positive Covid antibodies, elevated parvovirus IgG, elevated fungal markers and Candida in respiratory cultures. Secondary HLH due to sepsis or following COVID infection in the setting of malignancy was suspected. A course of antifungals and high dose steroids was given without improvement. Etoposide was considered, but avoided given possible sepsis, multiorgan failure and pancytopenia. A lymph node biopsy was performed with evidence of hemophagocytosis and ALK-positive anaplastic large cell lymphoma. Despite aggressive treatment, she developed progressive multiorgan failure resulting in death. Autopsy confirmed anaplastic large cell lymphoma with metastasis to the lymph nodes, lungs, epicardium and stomach. DISCUSSION: Malignancy is a known etiology of HLH in adults, however, few cases of ALK-positive anaplastic large cell lymphoma presenting as HLH have been reported. The rapid progression of HLH in this case stresses the importance of early diagnosis and treatment of HLH while pursuing an aggressive malignancy workup.

The Outcome in Cirrhosis after Hospital Discharge is Not Worsened with COVID-19 Infection: A Propensity Score-matched Analysis.

Background: Patients with cirrhosis and coronavirus disease-2019 (COVID-19) have high in-hospital mortality. The information on the outcome of cirrhosis patients in the posthospitalization period is limited. Aims: We aimed to study the outcome of cirrhosis patients with COVID-19 after hospital discharge. Methods: The records of the cirrhosis patients discharged after COVID-19 were reviewed. Their data were compared with a similar number of cirrhosis patients without COVID-19 after propensity score matching for age, sex, etiology of cirrhosis, and model for end-stage liver disease (MELD) score. Results: Cirrhosis patients with (n = 92) or without (n = 92) COVID-19 were included in 1:1 ratio. The mortality among COVID-19 (22; 23.9%) and non-COVID-19 (19; 20.7%) were comparable (HR 1.224; 95% CI 0.663-2.263, P = 0.520), over a similar duration of follow-up [186 (86-271) vs. 183 (103-274)]. Among COVID-19 patients, 45; 48.9% developed a new acute decompensation-increased ascites (40; 43.5%), hepatic encephalopathy (20; 21.7%), or variceal bleeding (8; 8.7%) whereas 25 (27.2%) patients needed rehospitalization. A proportion of participants continued to have either fatigue/weakness (24/80; 30.0%), sleep disturbances (11/80; 13.7%), or joint pains (16/80; 20.0%). The most common causes of death in patients of both groups were end-stage liver disease: 16 (72.7%) vs. 9 (47.4%), followed by multiorgan dysfunction: 4 (18.2%) vs. 6 (31.6%), GI bleeding: 2 (9.1%) vs. 4 (21.0%), P = 0.484. A lower albumin level, higher international normalized ratio, bilirubin, Child-Turcotte-Pugh, and MELD scores at discharge predicted mortality in the COVID-19 group. Conclusion: Short-term outcomes of patients with cirrhosis who survive the initial insult of COVID-19 are not different from patients without COVID-19, and survival is determined by the severity of liver disease at discharge.

Anaplastic Lymphoma Kinase-Positive Primary Lung Adenocarcinoma Presenting With Pericardial Effusion and Tamponade in a COVID-19 Patient: A Case Report.

Primary lung cancer usually presents in older adults with a smoking history. However, there is an estimated incidence of 15-20% among men who have never smoked. The diagnosis of lung malignancy can often be incidental. Moreover, cardiac tamponade can be an initial presentation of malignancy, especially lung cancer, as these are the most common tumors that involve the pericardium. Here, we present a 54-year-old male with no known medical history presented with dyspnea on exertion. He was found to have a large pericardial effusion with tamponade physiology on a bedside echocardiogram. He was also found to have bilateral deep vein thrombosis and pulmonary embolism on admission. The patient underwent an emergent pericardiocentesis due to hemodynamic compromise, and pericardial fluid cytology suggested adenocarcinoma with lung primary. Subsequently, gene testing revealed anaplastic lymphoma kinase-positive adenocarcinoma of the lung. The patient was discharged home with close oncology follow-up. It is imperative to recognize malignant pericardial effusion as one of the causes of dyspnea. Emergent pericardiocentesis may be needed in case of hemodynamic compromise and tenuous clinical status.

Predictors of in-hospital Outcomes in Patients With Cirrhosis and Coronavirus Disease-2019.

Background: Coronavirus disease-2019 (COVID-19) cases continue to increase globally. Poor outcomes in patients with COVID-19 and cirrhosis have been reported; predictors of outcome are unclear. The existing data is from the early part of the pandemic when variants of concern (VOC) were not reported. Aims: We aimed to assess the outcomes and predictors in patients with cirrhosis and COVID-19. We also compared the differences in outcomes between the first wave of pandemic and the second wave. Methods: In this retrospective analysis of a prospectively maintained database, data on consecutive cirrhosis patients (n = 221) admitted to the COVID-19 care facility of a tertiary care center in India were evaluated for presentation, the severity of liver disease, the severity of COVID-19, and outcomes. Results: The clinical presentation included: 18 (8.1%) patients had compensated cirrhosis, 139 (62.9%) acute decompensation (AD), and 64 (29.0%) had an acute-on-chronic liver failure (ACLF). Patients with ACLF had more severe COVID-19 infection than those with compensated cirrhosis and AD (54.7% vs. 16.5% and 33.3%, P < 0.001). The overall mortality was 90 (40.7%), the highest among ACLF (72.0%). On multivariate analysis, independent predictors of mortality were high leukocyte count, alkaline phosphatase, creatinine, child class, model for end-stage liver disease (MELD) score, and COVID-19 severity. The second wave had more cases of severe COVID-19 as compared to the first wave, with a similar MELD score and Child score. The overall mortality was similar between the two waves. Conclusion: Patients with COVID-19 and cirrhosis have high mortality (40%), particularly those with ACLF (72%). A higher leukocyte count, creatinine, alkaline phosphatase, Child class, and MELD score are predictors of mortality.

Drug interaction profile of TKI alectinib allows effective and safe treatment of ALK+ lung cancer in the kidney transplant recipient.

ALK targeting with tyrosine kinase inhibitors (TKIs) is a highly potent treatment option for the therapy of ALK positive non-small cell lung cancer (NSCLC). However, pharmacokinetics of TKIs leads to clinically significant drug interactions, and the interfering co-medication may hamper the anti-cancer therapeutic management. Here, we present for the first time a drug interaction profile of ALK-TKIs, crizotinib and alectinib, and immunosuppressive agent cyclosporine A in kidney transplant recipients diagnosed with ALK+ lung cancer. Based on therapeutic drug monitoring of cyclosporin A plasma level, the dose of cyclosporine A has been adjusted to achieve a safe and effective therapeutic level in terms of both cancer treatment and kidney transplant condition. Particularly, 15 years upon the kidney transplantation, the stage IV lung cancer patient was treated with the 1st-line chemotherapy, the 2nd-line ALK-TKI crizotinib followed by ALK-TKI alectinib. The successful therapy with ALK-TKIs has been continuing for more than 36 months, including the period when the patient was treated for COVID-19 bilateral pneumonia. Hence, the therapy of ALK+ NSCLC with ALK-TKIs in organ transplant recipients treated with cyclosporine A may be feasible and effective.

Novel fusion sarcomas including targetable NTRK and ALK.

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.

Constitutive PSGL-1 Correlates with CD30 and TCR Pathways and Represents a Potential Target for Immunotherapy in Anaplastic Large T-Cell Lymphoma.

Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoproliferative disorders and in multiple myeloma, it has been considered as a potential target for humoral immunotherapy, as well as an immune checkpoint inhibitor in T-cells. By investigating the expression of SELPLG in 678 T- and B-cell samples by gene expression profiling (GEP), further supported by tissue microarray and immunohistochemical analysis, we identified anaplastic large T-cell lymphoma (ALCL) as constitutively expressing SELPLG at high levels. Moreover, GEP analysis in CD30+ ALCLs highlighted a positive correlation of SELPLG with TNFRSF8 (CD30-coding gene) and T-cell receptor (TCR)-signaling genes (LCK, LAT, SYK and JUN), suggesting that the common dysregulation of TCR expression in ALCLs may be bypassed by the involvement of PSGL-1 in T-cell activation and survival. Finally, we evaluated the effects elicited by in vitro treatment with two anti-PSGL-1 antibodies (KPL-1 and TB5) on the activation of the complement system and induction of apoptosis in human ALCL cell lines. In conclusion, our data demonstrated that PSGL-1 is specifically enriched in ALCLs, altering cell motility and viability due to its involvement in CD30 and TCR signaling, and it might be considered as a promising candidate for novel immunotherapeutic approaches in ALCLs.

A qualitative study of online support communities for lung cancer survivors on targeted therapies.

BACKGROUND: Due to recent treatment advances, people who have non-small cell lung cancer with oncogenic alterations are an important new group of cancer survivors. Little is known about lung cancer online support communities. This research was guided by two primary questions: (1) How do these lung cancer survivors engage in online support communities? and (2) What are the psychological, social, and physical impacts of such engagement? METHODS: Qualitative in-depth interviews were conducted with patients with advanced lung cancer (N = 40) to learn about their experiences with the illness. We used qualitative thematic analysis, inductive and deductive, as outlined by Carspecken. We adapted the framework for studying online communities developed by Zhang and colleagues to examine engagement with and impacts of involvement in online lung cancer support communities. RESULTS: Participants described engaging in the online community through (1) initializing communication through asking questions or sharing resources, (2) responding to others comments or inquiries, or (3) simply observing/reading others posts. Participation had physical, psychological, or social impacts, with benefits (e.g., empowerment) and risks (e.g., feelings of jealousy or misinformation) in each domain. Participants used various strategies to mitigate negative impacts, such as distancing oneself as needed. CONCLUSIONS: Online lung cancer support communities provide support, camaraderie, and specialized health information. However, there are also risks of online engagement, such as social comparison or accessing misinformation. Understanding the utility of online support communities for lung cancer survivors on targeted therapies and further addressing their risks are urgent tasks, especially in the post-COVID era.

How Fear of COVID-19 Can Affect Treatment Choices for Anaplastic Large Cell Lymphomas ALK+ Therapy: A Case Report.

BACKGROUND: The t (2; 5) chromosomal rearrangement of the ALK gene with nucleophosmin 1 gene (NPM1), resulting in an NPM1-ALK fusion, was first demonstrated in 1994 in anaplastic large cell lymphoma, (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and the monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. RESULTS: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK+, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of brentuximab, still pending allo-SCT after two failed donor selections. Facing a new therapeutic failure, we requested and obtained authorization from the Italian drug regulatory agency to administer 250 mg of crizotinib twice a day, a drug incomprehensibly not registered for ALCL ALK +. CONCLUSIONS: The response to crizotinib was optimal since no adverse event occurred, and CT-PET scans persisted negative; this drug has proved to be a valid bridge to allo-SCT.

Genetic and Acquired Heterotopic Ossification: A Translational Tale of Mice and Men.

Heterotopic ossification is defined as an aberrant formation of bone in extraskeletal soft tissue, for which both genetic and acquired conditions are known. This pathologic process may occur in many different sites such as the skin, subcutaneous tissue, skeletal muscle and fibrous tissue adjacent to joints, ligaments, walls of blood vessels, mesentery and other. The clinical spectrum of this disorder is wide: lesions may range from small foci of ossification to massive deposits of bone throughout the body, typical of the progressive genetically determined conditions such as fibrodysplasia ossificans progressiva, to mention one of the most severe and disabling forms. The ectopic bone formation may be regarded as a failed tissue repair process in response to a variety of triggers and evolving towards bone formation through a multistage differentiation program, with several steps common to different clinical presentations and distinctive features. In this review, we aim at providing a comprehensive view of the genetic and acquired heterotopic ossification disorders by detailing the clinical and molecular features underlying the different human conditions in comparison with the corresponding, currently available mouse models.