Tabelecleucel for EBV+ PTLD following allogeneic HCT or SOT in a multicenter expanded access protocol.

Patients with Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disease (EBV+ PTLD) in whom initial treatment fails have few options and historically low median overall survival (OS) of 0.7 months following allogeneic hematopoietic cell transplant (HCT) and 4.1 months following solid organ transplant (SOT). Tabelecleucel is an off-the-shelf, allogeneic EBV-specific cytotoxic T-lymphocyte immunotherapy for EBV+ PTLD. Previous single-center experience showed responses in patients with EBV+ PTLD following HCT or SOT. We now report outcomes from a multicenter expanded access protocol (NCT02822495) in HCT (n = 14) and SOT (n = 12) recipients treated with tabelecleucel for EBV+ PTLD that was relapsed/refractory to rituximab ± chemotherapy. The investigator-assessed objective response rate was 65.4% overall (including 38.5% with a complete and 26.9% with a partial response), 50.0% in HCT, and 83.3% in SOT. The estimated 1- and 2-year OS rates (95% CI) were both 70.0% (46.5, 84.7) overall, both 61.5% (30.8, 81.8) in HCT, and both 81.5% (43.5, 95.1) in SOT (median follow-up: 8.2, 2.8, and 22.5 months, respectively). Patients responding to tabelecleucel had higher 1- and 2-year OS rates (94.1%) than non-responders (0%). Treatment was well tolerated with no reports of tumor flare, cytokine release syndrome, or rejection of marrow and SOT. Results demonstrate clinically meaningful outcomes across a broad population treated with tabelecleucel, indicating a potentially transformative and accessible treatment advance for relapsed/refractory EBV+ PTLD following HCT or SOT.

Ophthalmologic profile of patients with systemic sclerosis.

PURPOSE: To study the ophthalmologic manifestations of systemic sclerosis (SSc) and its correlation with autoantibody profile. METHODS: A cross-sectional study on 200 eyes of 100 consecutive adult patients diagnosed with SSc was performed at a tertiary care center in Northern India. The examination of ocular adnexa, anterior segment, and posterior segment with slit-lamp biomicroscopy, tear film break-up time (TBUT), Schirmer's II test, and choroidal thickness measurement by swept-source ocular coherence tomography was done. Autoantibody profile was available for 85 patients, and its statistical association with the ocular examination findings was analyzed. RESULTS: In total, 100 patients (93 females and 7 males) were included. The mean age was 45.11 ± 11.68 years, and the mean disease duration was 6.93 ± 3.68 years. Meibomian gland disease was more commonly found in patients with the diffuse subtype of SSc (P = 0.037). Choroidal thickness was increased in 34% and decreased in 7% (reference range = 307 ± 79 mm) patients. Reduced TBUT, meibomian gland dysfunction, and eyelid stiffness had a statistically significant association with the presence of anti-Scl-70 antibody (P = 0.003, <0.0001, and 0.004, respectively). These patients had ocular fatigue, foreign body sensation, and burning sensation. No significant association was noted with the presence of SS-A/Ro and SS-B/La antibodies. CONCLUSION: This study highlights the need for an active comprehensive ophthalmic evaluation. Approximately 75% of the patients in our cohort had ocular involvement to varying extent. An isolated presence of anti-Scl70 antibody was also found to have a positive association with dry eye disease.

Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial.

BACKGROUND: Survival in Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disease following haematopoietic stem-cell transplant (HSCT) or solid organ transplant (SOT) is poor after failure of initial therapy, indicating an urgent need for therapies for this ultra-rare disease. With recent EU marketing authorisation, tabelecleucel is the first off-the-shelf, allogeneic, EBV-specific T-cell immunotherapy to receive approval for treatment of relapsed or refractory EBV-positive post-transplant lymphoproliferative disease. We aimed to determine the clinical benefit of tabelecleucel in patients with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease following HSCT or SOT. METHODS: In this global, multicentre, open-label, phase 3 trial, eligible patients (of any age) had biopsy-proven EBV-positive post-transplant lymphoproliferative disease, disease that was relapsed or refractory to rituximab after HSCT and rituximab with or without chemotherapy after SOT, and partially HLA-matched and appropriately HLA-restricted tabelecleucel available. Patients received tabelecleucel administered intravenously at 2 × 106 cells per kg on days 1, 8, and 15 in 35-day cycles and are assessed for up to 5 years for survival post-treatment initiation. The primary endpoint was objective response rate. All patients who received at least one dose of tabelecleucel were included in safety and efficacy analyses. This trial is registered with ClinicalTrials.gov, NCT03394365, and is ongoing. FINDINGS: From June 27, 2018, to Nov 5, 2021, 63 patients were enrolled, of whom 43 (24 [56%] male and 19 [44%] female) were included, 14 had prior HSCT, 29 had SOT. Seven (50%, 95% CI 23-77) of 14 participants in the HSCT group and 15 (52%, 33-71) of 29 participants in the SOT group had an objective response, with a median follow-up of 14·1 months (IQR 5·7-23·9) and 6·0 months (1·8-18·4), respectively. The most common grade 3 or 4 treatment-emergent adverse events were disease progression (in four [29%] of 14 in HSCT and eight [28%] of 29 in SOT) and decreased neutrophil count (in four [29%] of 14 in HSCT and four [14%] of 29 in SOT). Treatment-emergent serious adverse events were reported in 23 (53%) of 43 patients and fatal treatment-emergent adverse events in five (12%); no fatal treatment-emergent adverse event was treatment-related. There were no reports of tumour flare reaction, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, transmission of infectious diseases, marrow rejection, or infusion reactions. No events of graft-versus-host disease or SOT rejection were reported as related to tabelecleucel. INTERPRETATION: Tabelecleucel provides clinical benefit in patients with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease, for whom there are no other approved therapies, without evidence of safety concerns seen with other adoptive T-cell therapies. These data represent a potentially transformative and accessible treatment advance for patients with relapsed or refractory disease with few treatment options. FUNDING: Atara Biotherapeutics.

Analytical techniques for the characterization of nanoparticles for mRNA delivery.

Nanotechnology-assisted RNA delivery has gotten a tremendous boost over the last decade and made a significant impact in the development of life-changing vaccines and therapeutics. With increasing numbers of emerging lipid- and polymer-based RNA nanoparticles progressing towards the clinic, it has become apparent that the safety and efficacy of these medications depend on the comprehensive understanding of their critical quality attributes (CQAs). However, despite the rapid advancements in the field, the identification and reliable quantification of CQAs remain a significant challenge. To support these efforts, this review aims to summarize the present knowledge on CQAs based on the regulatory guidelines and to provide insights into the available analytical characterization techniques for RNA-loaded nanoparticles. In this context, routine and emerging analytical techniques are categorized and discussed, focusing on the operation principle, strengths, and potential limitations. Furthermore, the importance of complementary and orthogonal techniques for the measurement of CQAs is discussed in order to ensure the quality and consistency of analytical methods used, and address potential technique-based differences.

Postoperative Closed-Suction Drain in Anterior Orbitotomy.

Purpose To evaluate the role of a closed-suction drain in orbital mass excision following anterior orbitotomy. Methods This is a prospective, randomized comparative study of consecutive patients undergoing anterior orbitotomy and mass excision enrolled into two groups: group A (with drain) and group B (without drain). Clinical data included visual acuity assessment, proptosis measured by exophthalmometry, pain score assessment, eyelid swelling, and ocular motility. Postoperative data were compared for one to five days and at 14 and 30-day follow-ups in the two groups to evaluate the efficacy of closed-suction drain in orbital mass excision. Results Twenty-five patients planned for anterior orbitotomy were divided into two groups: group A (drain, n = 12) and group B (without drain, n = 13). The subsidence of proptosis (p = 0.041), eyelid swelling (p = 0.04), and restoration of ocular motility (p = 0.04) were faster in the drain group as compared to the non-drain group, which was observed as statistically significant. The outcomes at 30 days were comparable in both groups and none of the patients developed any long-term complications. Conclusion The use of orbital drains aids early postoperative recovery with faster subsidence of proptosis and eyelid edema, and rapid recovery of ocular movements but does not affect the final outcome. Orbital surgeons can individualize the use of closed-suction drains after anterior orbitotomy in cases with expected postoperative edema.

Sinonasal schwannoma masquerading as an IgG4-related nasal mass.

An elderly (8th decade) diabetic patient presented with insidious, painless protrusion of the right eye for 1 month, associated with nasal congestion. Past history included healed serous chorioretinopathy in the right eye (>30 years back) and recently diagnosed (1 year prior) autoimmune IgG4-related pancreatitis for which he was on long-term corticosteroids. On nasal endoscopic examination, a well circumscribed mass was found in the right nasal cavity.Keeping in mind the systemic diagnosis, the sinonasal mass was suspected to be a IgG4-related disease. An endoscopic biopsy was performed and revealed a surprise diagnosis of grade 1 nasal schwannoma.

Preliminary results from the EMoLung clinical study showing early lung cancer detection by the LC score.

BACKGROUND: Lung cancer (LC) causes more deaths worldwide than any other cancer type. Despite advances in therapeutic strategies, the fatality rate of LC cases remains high (95%) since the majority of patients are diagnosed at late stages when patient prognosis is poor. Analysis of the International Association for the Study of Lung Cancer (IASLC) database indicates that early diagnosis is significantly associated with favorable outcome. However, since symptoms of LC at early stages are unspecific and resemble those of benign pathologies, current diagnostic approaches are mostly initiated at advanced LC stages. METHODS: We developed a LC diagnosis test based on the analysis of distinct RNA isoforms expressed from the GATA6 and NKX2-1 gene loci, which are detected in exhaled breath condensates (EBCs). Levels of these transcript isoforms in EBCs were combined to calculate a diagnostic score (the LC score). In the present study, we aimed to confirm the applicability of the LC score for the diagnosis of early stage LC under clinical settings. Thus, we evaluated EBCs from patients with early stage, resectable non-small cell lung cancer (NSCLC), who were prospectively enrolled in the EMoLung study at three sites in Germany. RESULTS: LC score-based classification of EBCs confirmed its performance under clinical conditions, achieving a sensitivity of 95.7%, 91.3% and 84.6% for LC detection at stages I, II and III, respectively. CONCLUSIONS: The LC score is an accurate and non-invasive option for early LC diagnosis and a valuable complement to LC screening procedures based on computed tomography.

An In Vitro Approach to Model EMT in Breast Cancer.

During the progression from ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC), cells must overcome the physically restraining basement membrane (BM), which compartmentalizes the epithelium from the stroma. Since the extracellular matrix (ECM) of the epithelial and stromal compartments are biochemically and physically distinct from one another, the progression demands a certain degree of cellular plasticity for a primary tumor to become invasive. The epithelial-to-mesenchymal transition (EMT) depicts such a cell program, equipping cancer cells with features allowing for dissemination from the epithelial entity and stromal invasion at the single-cell level. Here, the reciprocal interference between an altering tumor microenvironment and the EMT phenotype was investigated in vitro. BM-typical collagen IV and stroma-typical collagen I coatings were applied as provisional 2D matrices. Pro-inflammatory growth factors were introduced to improve tissue mimicry. Whereas the growth on coated surfaces only slightly affected the EMT phenotype, the combinatorial action of collagen with growth factor TGF-ß1 induced prominent phenotypic changes. However, EMT induction was independent of collagen type, and cellular accessibility for EMT-like changes was strongly cell-line dependent. Summarizing the entire body of data, an EMT-phenotyping model was used to determine cellular EMT status and estimate EMT-like changes. The miR200c-mediated reversion of mesenchymal MDA-MB-231 cells is reflected by our EMT-phenotype model, thus emphasizing its potential to predict the therapeutic efficacy of EMT-targeting drugs in the future.

Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer.

Background: Small cell lung cancer (SCLC) is an extremely aggressive cancer type with a patient median survival of 6-12 months. Epidermal growth factor (EGF) signaling plays an important role in triggering SCLC. In addition, growth factor-dependent signals and alpha-, beta-integrin (ITGA, ITGB) heterodimer receptors functionally cooperate and integrate their signaling pathways. However, the precise role of integrins in EGF receptor (EGFR) activation in SCLC remains elusive. Methods: We analyzed human precision-cut lung slices (hPCLS), retrospectively collected human lung tissue samples and cell lines by classical methods of molecular biology and biochemistry. In addition, we performed RNA-sequencing-based transcriptomic analysis in human lung cancer cells and human lung tissue samples, as well as high-resolution mass spectrometric analysis of the protein cargo from extracellular vesicles (EVs) that were isolated from human lung cancer cells. Results: Our results demonstrate that non-canonical ITGB2 signaling activates EGFR and RAS/MAPK/ERK signaling in SCLC. Further, we identified a novel SCLC gene expression signature consisting of 93 transcripts that were induced by ITGB2, which may be used for stratification of SCLC patients and prognosis prediction of LC patients. We also found a cell-cell communication mechanism based on EVs containing ITGB2, which were secreted by SCLC cells and induced in control human lung tissue RAS/MAPK/ERK signaling and SCLC markers. Conclusions: We uncovered a mechanism of ITGB2-mediated EGFR activation in SCLC that explains EGFR-inhibitor resistance independently of EGFR mutations, suggesting the development of therapies targeting ITGB2 for patients with this extremely aggressive lung cancer type.

Targeted GATA3 knockdown in activated T cells via pulmonary siRNA delivery as novel therapy for allergic asthma.

GATA3 gene silencing in activated T cells displays a promising option to early-on undermine pathological pathways in the disease formation of allergic asthma. The central transcription factor of T helper 2 (Th2) cell cytokines IL-4, IL-5, and IL-13 plays a major role in immune and inflammatory cascades underlying asthmatic processes in the airways. Pulmonary delivery of small interfering RNAs (siRNA) to induce GATA3 knockdown within disease related T cells of asthmatic lungs via RNA interference (RNAi) presents an auspicious base to realize this strategy, however, still faces some major hurdles. Main obstacles for successful siRNA delivery in general comprise stability and targeting issues, while in addition the transfection of T cells presents a particularly challenging task itself. In previous studies, we have developed and advanced an eligible siRNA delivery system composed of polyethylenimine (PEI) as polycationic carrier, transferrin (Tf) as targeting ligand and melittin (Mel) as endosomolytic agent. Resulting Tf-Mel-PEI polyplexes exhibited ideal characteristics for targeted siRNA delivery to activated T cells and achieved efficient and sequence-specific gene knockdown in vitro. In this work, the therapeutic potential of this carrier system was evaluated in an optimized cellular model displaying the activated status of asthmatic T cells. Moreover, a suitable siRNA sequence combination was found for effective gene silencing of GATA3. To confirm the translatability of our findings, Tf-Mel-PEI polyplexes were additionally tested ex vivo in activated human precision-cut lung slices (PCLS). Here, the formulation showed a safe profile as well as successful delivery to the lung epithelium with 88% GATA3 silencing in lung explants. These findings support the feasibility of Tf-Mel-PEI as siRNA delivery system for targeted gene knockdown in activated T cells as a potential novel therapy for allergic asthma.

Long-term Surgical Outcomes in Patients of Centurion Syndrome: A Mystic Etiology of Epiphora in Young.

AIM: To describe the clinical features and long-term outcomes of the medial canthal tendon (MCT) release procedure in patients with Centurion Syndrome (CS). METHODS: We performed a retrospective analysis of the diagnosed patients with CS from July 2013 to December 2019. CS was diagnosed clinically based on the anterior displacement of MCT, anterior dislocation of lacrimal punctum out of tear lake, prominent nasal bridge, beak sign, and synophyrs. All symptomatic patients were advised the anterior limb of MCT release with modified closure of the skin incision. The outcome measures were based on Munk's score (subjective) and the fluorescein dye disappearance test (objective). A minimum postoperative follow-up of 12 months was an inclusion criterion. RESULTS: We studied 22 patients (44 eyes) having a median age of 14.5 years. Anteriorly displaced MCT and lacrimal punctum were noted in 44 eyes (100%), prominent nasal bridge in 20 patients (90.9%), beak sign in 36 eyes (81.8%), and synophyrs in 17 (77.3%) patients. All 44 eyes underwent MCT release with adjunctive punctoplasty (n = 6 eyes) or lower eyelid retractor plication (n = 4 eyes). At a mean follow-up of 12.6 months, 26 eyes (59.1%) showed complete response, i.e., negative FDDT and grade 0 Munk score. Partial response was noted in 14 (31.8%) eyes, i.e., delayed FDDT and reduction of ≥2 grades on Munk score. CONCLUSION: Along with the classic features of CS, beak sign and synophyrs are important diagnostic ophthalmic-facial features of CS. The transverse closure of surgical wounds may provide effective long-term benefits in the medial canthal tendon release procedure.

Cadaver dissection for oculoplastic procedures: A beginner's guide.

The purpose of this article is to form a basic guide for beginning the cadaver dissection training programs focused on oculoplastic surgical procedures. Ours was a collaborative study between the departments of Ophthalmology and Anatomy in a tertiary care teaching institute. We formed a step-wise approach to begin the cadaver dissection focused on the oculoplastic surgical procedures. The basics of cadaver procurement, processing, and preparation for dissections were described. The operative requirements of trainees, surgical handling of cadavers, and basic oculoplastic surgical steps were discussed. The types of embalming (cadaver preservation process) and steps have been described in detail. We have emphasized the preoperative discussion about the proposed dissections using standard teachings and skull models for easier understanding. Additional helping tools like soft embalming and injectable substances for better intra-dissection understanding (intra-arterial, intravenous and orbital injections) have been described. Post-dissection cadaver handing and soft-tissue disposal protocols have also been described. Overall, the cadaver dissections provide holistic surgical learning for the residents, specialty trainees, and practitioners. This article may act as a basic step-wise guide for starting the cadaver-based oculoplastics lab dissection in various institutes and workshops.

Endoscope Assisted Combined Drainage of Sino-Orbital Abscess: Technique Revisited.

Orbital complications of acute rhinosinusitis may present with painful proptosis and ophthalmoplegia. Surgical management, when required comprises of endonasal endoscopic sinus clearance with or without external orbital abscess drainage. External drainage involves blind dissection and carries a risk of iatrogenic injury to periorbital structures. We describe a novel technique of endoscope guided orbital abscess drainage under direct visualisation via the external incision site. Patients with orbital cellulitis secondary to rhinosinusitis and planned for surgical intervention were recruited. After endonasal endoscopic sinus surgery, the orbital abscess cavity was opened and an endoscope was inserted externally. The cavity was examined; loculi were opened under direct visualisation till drainage was complete. This procedure was performed in seven patients with a successful outcome. The mean time to resolution was 1.5 months (36.4 ± 18.2 days). None of the patients had any recurrence or residual disease on follow up. In addition, in two cases with obstructed sinus drainage and "walling off" of frontal sinus, visualisation of the instrument placed in the drained abscess cavity via endo-nasally inserted endoscope confirmed the re-establishment of continuity of sinus opening. This approach may allow the surgeon to drain multiloculated abscess completely under direct visualization while minimising iatrogenic damage to periorbital structures. Real time display using endoscopic camera on the monitor screen also serves as a teaching and training tool during the procedure. Technique utilises the existing endoscopic set-up without the need for additional instrumentation.

Long-term outcomes of lacrimal canalicular trephination with viscoelastic-assisted monocanalicular stenting for canalicular obstructions.

Purpose: To study the long-term outcomes of lacrimal canalicular trephination (LCT) with viscoelastic-assisted monocanalicular stenting (VAMS) for the treatment of epiphora secondary to lacrimal canalicular obstructions (LCO). Methods: Our study was a retrospective interventional work. All patients diagnosed with LCO, having morbid epiphora (Munk's scale ≥ 2), were included. The LCO was divided as proximal (< 6mm from punctum) and distal (≥ 6mm from punctum). Sisler's lacrimal trephine (21 gauge) was used to recanalize the LCO with monocanalicular stent (0.64mm diameter) insertion, which was kept for a minimum of 6 weeks and a post-stent removal follow-up of 12 months was ensured. Fluorescein dye disappearance test and lacrimal irrigation were used as functional and anatomical tests for evaluation, respectively. Results: We included 73 eyes of 52 patients having a mean age of 44.5 years. Of the total, the proximal LCO was seen in 38 eyes (52.1%) and distal in 35 eyes (47.9%). The preoperative Munk's score of 5 was noted in the majority (n=57 eyes, 78.1%). The majority (n=32 eyes, 43.8%) had chronic blepharitis or meibomian gland disease as etiology. Monocanalicular stent was kept in place for a mean of 13.5 weeks. At a mean follow-up of 14.5 months, complete response was noted in 35.6% cases, while 50.7% had partial and 13.7% had a failure of the procedure. Conclusions: LCT (without DCR) is a minimally invasive, simple, and effective technique for the treatment of LCO in the long term. VAMS is a helpful innovation to facilitate the insertion of the flexible silicone stent.

Evaluation of lacrimal duct probing in adults with 0.02% and 0.04% mitomycin-C in primary acquired nasolacrimal duct obstruction: A randomized comparative pilot study.

PURPOSE: The purpose of the study is to evaluate the safety and efficacy of adjunctive use of mitomycin-C (MMC) using two different concentrations 0.2 mg/ml and 0.4 mg/ml for lacrimal duct probing to treat the nasolacrimal duct obstruction (NLDO) in adults. SUBJECTS AND METHODS: Prospective, an interventional comparative randomized pilot study of lacrimal duct probing conducted in the two study groups 0.02% MMC group (n = 30) and 0.04% MMC group (n = 30) in confirmed primary acquired NLDO of <1-year duration. Patency of lacrimal duct probing confirmed by syringing was compared at 1, 3, and 6-month follow-up in the two study groups, and corresponding subjective improvement of watering was appraised according to Kraft and Crawford grading. RESULTS: Patency of lacrimal duct probing in 0.02% MMC versus 0.04% MMC group was 66.66%/73.33% (P = 0.71) at 1 month, 46.66%/66.66% (P = 0.09) at 3 months and 46.66%/66.66% (P = 0.03) at 6-month follow-up, respectively. Subjective improvement of watering (no watering and mild watering) observed in 0.02% MMC versus 0.04% MMC group was 46.66%/73.33% (P = 0.03), at 1 month, 66.66%/83.33% (P = 0.13) at 3 months and 56.66%/73.33% (P = 0.17) at 6-month follow-up. CONCLUSION: Adult lacrimal duct probing with 0.04% MMC was associated with significant higher objective success rate than adult lacrimal duct probing with 0.02% MMC, without added concurrently side effects.

A "Clinical Tetrad" for Easy Diagnosis of Lacrimal Canaliculitis.

Purpose: To study the clinical presentation and highlight the "diagnostic clinical features" in patients having lacrimal canaliculitis (LC). Methods: A retrospective analysis of all patients diagnosed with primary and secondary LC was performed. A detailed slit-lamp examination of the conjunctiva, lacrimal punctum, canalicular region, and lacrimal sac was performed. Common and coexisting clinical features were highlighted. The posttreatment sequence of resolution of clinical features was also noted. Results: Forty eyes of 36 patients (28 females, 77.78%) with a mean age of 59.5 years were included in the study. Thirty eyes (75%) had primary LC, whereas 10 had a secondary type. Previous misdiagnoses were noted in 34 (85%) eyes. The highlighting clinical features were medial eyelid edema (n = 40, 100%), pouting and hyperemia of lacrimal punctum (n = 36, 90%), yellowish canalicular hue (n = 35, 87.5%), and canalicular distention and expressible discharge (n = 32, 80%). None had features suggestive of nasolacrimal duct obstruction. Thirty-two eyes (80%) showed all four clinical features of LC, a tetrad. At a mean follow-up of 14.5 months, the complete resolution was noted in 36 (90%) eyes. Conclusions: We propose a "clinical tetrad" of 1. medial eyelid edema, 2. pouting and hyperemia of lacrimal punctum, 3. yellowish canalicular hue and, 4. canalicular distention, and expressible discharge, for the easier clinical diagnosis of LC. The authors believe that using this clinical tetrad may be helpful for the diagnosis of LC.

Feasibility of Cognitive Training to Promote Recovery in Cancer-Related Cognitive Impairment in Adolescent and Young Adult Patients.

Background: Computer-based cognitive rehabilitation programs may help adolescent and young adult (AYA) patients with cancer-related cognitive impairment. This pilot study investigated the feasibility of cognitive rehabilitation as a preventive intervention for AYA patients receiving chemotherapy. Explorative objectives included the correlation of cognitive performance with serum brain-derived neurotrophic factor (BDNF). Methods: This pilot prospective study included English-speaking patients 12-25 years of age with a fist diagnosis of cancer requiring chemotherapy. Participants enrolled in the intervention arm participated in a computer-based neurocognitive training program for 20-30 minutes daily for 16 weeks. Outcome measures, including engagement with and completion of computerized neurocognitive testing and serum BDNF levels, were obtained within the first month following diagnosis, ∼16 and 24 weeks from enrollment. Results: Fourteen of 18 eligible patients provided consent, with 7 patients assigned to each the intervention arm and nonintervention arm. Seventy-one percent of the patients in the intervention arm completed at least 80% of the required activities. Compared to baseline, patients in the nonintervention arm demonstrated higher prevalence of impairment in four of the six cognitive domains (processing speed, visual attention, attention/working memory, and executive function) at the end of the study period. There was a nonstatistically significant reduction of serum BDNF levels over time, which was observed in both intervention and nonintervention arms. Conclusion: This pilot study provides some evidence that it is feasible for AYAs with new cancer diagnoses to receive standardized cognitive rehabilitation. Patients receiving cognitive activities experienced less impairment in numerous cognitive domains.

Waldenström Macroglobulinemia of the orbit: A diagnostic challenge.

PURPOSE: Ocular adnexal lymphomas (OAL) constitute 55% of all orbital tumors. Waldenström Macroglobulinemia (WM) presenting as an orbital mass with diffuse extraocular muscle (EOM) involvement is rare. We report an elderly patient who presented to the ophthalmologist for an orbital mass which on evaluation, turned out to an ocular adnexal WM. OBSERVATIONS: A 75 years old man presented with a palpable mass in the left anterior superior orbit and bilateral restricted ocular motility in all gazes. Computed tomography scan revealed a hyperdense mass with diffuse thickening of extraocular muscles and enlarged lacrimal gland on the left side. Incisional biopsy of the mass revealed a lymphoproliferative neoplasm with plasmacytic morphology. Immunohistochemistry (IHC) of the orbital mass as well as the bone marrow was sought, lymphoplasmacytic lymphoma (CD20+, CD38+, MUM1+, BCL 2+, CD3-, CD5-, CD10-, CD23-, cyclin D1). Bone marrow flow cytometry showed CD5-, CD10- kappa restricted B cell neoplasm. Serum analysis significantly elevated IgM levels. This indicated a diagnosis of ocular adnexal Waldenström Macroglobulinemia. CONCLUSION AND IMPORTANCE: This case highlights the importance of clinical evaluation, histopathology, and immunohistochemistry for phenotyping of ocular adnexal lymphomas.