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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ravaged the global society as we know it. As almost a dozen pharmaceutical agents go into randomized controlled clinical trials, multiple studies have surfaced trying to associate a hypercoagulable state to coronavirus disease 2019 (COVID-19) patients. We report two COVID-19 cases who presented with occlusive pulmonary embolism (PE) strongly supporting a hypercoagulable state incurred by SARS-CoV-2. This is significant as it is one of the early reports of such an initial presentation of COVID-19 in the USA. Through our report, we invite the medical community to share a perspective about long-term management guidelines for SARS-CoV-2 associated venous thromboembolism (VTE) and prompt future research.

Bismuth and antimony-based chalcogenides have been extensively publicized in recent years owing to their intrinsic characteristics and inherent topological character. Such a system contains Bi2Se3, Bi2Te3, Sb2Te3, etc. The single crystalline facets of these samples were discovered to have a generation of ~2 THz while having a giant magneto-resistance of around ~300%. These inherent and dynamical features of the system make it resilient for several applications in optoelectronics and spintronics. The temperature-dependent assessment of conductivity, terahertz generation, and charge carrier dynamics aids in understanding the fundamental phenomena in the carrier mechanism of the chalcogenides. This chapter contains the essential fundamental knowledge of the single crystal chalcogenides via charge carrier & phonon dynamics and their response in the terahertz frequency domain.

Background Gall bladder cancer (GBC) is the fifth most common malignancy in the gastrointestinal system and the most common malignancy of the biliary system. GBC is a very aggressive malignancy having a 5 year survival rate of 19%. Giant Gall Bladder (GGB) is an uncommon condition that can result from cholelithiasis or chronic cholecystitis and rarely with malignancy. Case report A 65 year old lady presented with vague abdominal pain for 12 years and right abdominal lump of size 20 × 8 cms was found on examination. CT scan showed a circumferentially irregularly thickened wall (2.5 cm) of gall bladder indicative of malignancy. Per-operatively a GB of size 24 × 9 cm was noted and patient underwent radical cholecystectomy. It was surprise to find such a giant malignant GB with preserved planes. Histopathology, it was well differentiated adenocarcinoma of gall bladder of Stage II (T2a N0 M0). Discussion It is known that mucocoele of GB can attain large size, however chronic cholecystitis will lead to a shrunken gall bladder rather than an enlarged one. A malignant GB of such size and resectable is rare without any lymph node involvement or liver infiltration. Few cases of giant benign gall bladder have been reported in literature, however this appears to be the largest resectable gall bladder carcinoma reported till date as per indexed literature. Conclusion Giant GB is an uncommon finding. They are mostly benign, however malignant cases can occur. Radiological findings may suggest features of malignancy and define extent of disease. Prognosis depends on stage of disease and resectability, irrespective of size.

Background: Gall bladder cancer (GBC) is the fifth most common malignancy in the gastrointestinal system and the most common malignancy of the biliary system. GBC is a very aggressive malignancy having a 5 year survival rate of 19%. Giant Gall Bladder (GGB) is an uncommon condition that can result from cholelithiasis or chronic cholecystitis and rarely with malignancy.Case report: A 65 year old lady presented with vague abdominal pain for 12 years and right abdominal lump of size 20x8 cms was found on examination. CT scan showed a circumferentially irregularly thickened wall (2.5cm) of gall bladder indicative of malignancy. Per-operatively a GB of size 24 x 9 cms was noted and patient underwent radical cholecystectomy. It was surprise to find such a giant malignant GB with preserved planes. Histopathology, it was well differentiated adenocarcinoma of gall bladder of Stage II (T2a N0 M0). Discussion: It is known that mucocoele of GB can attain large size, however chronic cholecystitis will lead to a shrunken gall bladder rather than an enlarged one. A malignant GB of such size and resectable is rare without any lymph node involvement or liver infiltration. Few cases of giant benign gall bladder have been reported in literature, however this appears to be the largest resectable gall bladder carcinoma reported till date as per indexed literature.Conclusion: Giant GB is an uncommon finding. They are mostly benign, however malignant cases can occur. Radiological findings may suggest features of malignancy and define extent of disease. Prognosis depends on stage of disease and resectability, irrespective of size.

Background Treatment of solid malignancies has been revolutionized with the introduction of immune checkpoint inhibitors (ICIs) and their use is being expanded in therapy of different cancers. However, immune related adverse events (IRAEs) can occur during treatment. These side effects occur due to stimulation of the innate and adaptive immune system and can lead to serious complications. Recently, acral ischemia has been reported in some cases during treatment with programmed death-1 (PD-1) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitors. Here, we discuss a case in which acral necrosis developed after initiation of a PD-1 inhibitor. We offer a review of the existing literature on the pathophysiology, clinical course and treatment outcomes. Case presentation A 68-year-old female was diagnosed with stage IV non-small cell lung adenocarcinoma and was started on pembrolizumab. The patient developed sudden onset numbness and discoloration of fingertips bilaterally at week 25 after initiation of ICI treatment. Extensive workup to rule out hypercoagulable, autoimmune and vascular disease was unremarkable except for mild elevation of ANA and ESR. The symptoms quickly progressed into dry gangrene within four weeks and did not respond to medical or surgical treatment. Pembrolizumab was subsequently discontinued due to progression of metastatic disease. The patient refused further interventions and transitioned to hospice care where she expired after two months. Conclusion Acral ischemia can develop during treatment of malignancies. This complication, although uncommon, canresult in digital amputation. Physicians should be aware of the possible progression of acral vascular necrosis when Raynaud’s like symptoms develop. Larger studies are needed to confirm the role of ICIs in the pathogenesis of acral vascular necrosis.

The flux pinning properties of the high temperature superconductor YBa2Cu3O7−δ (YBCO) have been conventionally improved by creating both columnar and dot-like pinning centres into the YBCO matrix. To study the effects of differently doped multilayer structures on pinning, several samples consisting of a multiple number of individually BaZrO3 (BZO) and BaCeO3 (BCO) doped YBCO layers were fabricated. In the YBCO matrix, BZO forms columnar and BCO dot-like defects. The multilayer structure improves pinning capability throughout the whole angular range, giving rise to a high critical current density, J c. However, the BZO doped monolayer reference still has the most isotropic J c. Even though BZO forms nanorods, in this work the samples with multiple thin layers do not exhibit a c axis peak in the angular dependence of J c. The angular dependencies and the approximately correct magnitude of J c were also verified using a molecular dynamics simulation.

Abstract 1880 AL is a clonal plasma cell disorder with a reported median survival (OS) of 13 months from diagnosis. Therapy involves suppression of amyloidogenic light chain production from clonal plasma cells. Hematological response (HR) is critical to improve organ function and survival. Autologous transplantation (AHCT) despite its risks, if performed in expert centers leads to rapid HR and organ function improvement. Those with poor Karnofsky performance score (KPS), multisystem disease or cardiac AL are poor candidates for AHCT. We assessed the efficacy of bortezomib (V) based combination therapy in newly diagnosed AL in a population with poor KPS or ineligible for AHCT. Among 35 consecutive newly diagnosed, biopsy proven AL patients (pts) since 2006, 29 pts received at least 2 cycles of V based therapy and were evaluable. Non evaluable pts (n=6) did not complete 2 cycles of therapy: liver function abnormalities (1), neuropathy (1); or early death (4 within 6 weeks of diagnosis). Two treatment protocols were used sequentially over this period. From 2006 – 4/2009, V twice weekly with dexamethasone weekly (VD) for 2 out of 3 weeks (n= 14) and thereafter weekly VD with cyclophosphamide (CVD) x3 on a q 4 week schedule (n=15). For complete or partial responses (CR/PR) after 6 cycles of therapy, V maintenance was administered every 2 weeks. Response evaluation was according to the 10th international AL symposium criteria. Results: Median age was 68 years (range 35–88 years; 55% female). Subtype of AL was lambda in 55%. KPS was less than 80 in more than 50%. Majority had 3 or more organs involved: 62% cardiac, 62% renal, 41% GI, 20% neurologic and 17% liver involvement. Cardiac stage was Mayo III in 50%. Hematological response (HR) was achieved in 86% including 34% CR and 52% PR. Among non-responders (14%), 2 have died after 2 cycles and 1 discontinued therapy. Median number of cycles to achieve a HR was 3 cycles (range, 1 to 9 cycles). CR was achieved after a median of 4 cycles for VD and 3 cycles for CVD. At median follow up of 22 mo (range 2–57 mo), median overall and progression free (PFS) survival have not been reached. Median OS for patients with cardiac involvement (n= 18) was 11 mo (range 2 – 29 mo). Among those with HR, 60% had at least one organ response including 44% renal and 55% cardiac responses. Among those with HR, 2 died following hematological progression; while 6 died of AL related organ failure. Half the deaths due to AL organ dysfunction were within the first 4 cycles. Median duration of response has not been reached. Hematopoietic cell harvest was successful in 41% (n=12) of which 4 pts completed consolidative AHCT. There was no difference in survival between those achieving CR vs. PR (log rank p = 0.5, Fig 1) or between recipients of CVD vs. VD (log rank p= 0.47 and Table 1). Therapy related non-hematologic adverse effects (all grades) included peripheral neuropathy (27%), gastrointestinal events with nausea, vomiting and diarrhea (17%), infections (3%) and blood clots (3%). Grade ≥ 3 toxicities were 3% and discontinuations/dose reductions resulting from toxicities were 10% and 3% respectively. Worsening of preexisting neuropathy was rare (2 pts out of 6). In this cohort of advanced multisystem AL with poor KPS; VD or CVD established rapid responses in 86%. In comparison with upfront AHCT, this approach has the advantages of lower toxicity, wider applicability and similar response time although durability of response is unknown at this time. Stem cell harvest was feasible when attempted. Addition of cyclophosphamide was well tolerated with the benefit of rapid onset of CR and allowed once weekly V without compromising efficacy. In good risk pts, AHCT should be compared against CVD in prospective randomized fashion. Disclosures: No relevant conflicts of interest to declare.

Abstract 5097 Background: The uniform response criteria for MM suggest that in clinical practice early biochemical progression (EBP) of MM and clinical relapse (clinREL) be distinguished to identify symptomatic patients requiring therapy. The interval between EBP and clinREL in MM is not well characterized. Biochemical progression in those with intact immunoglobulin MM (IIM) could involve serum free light chain (SFLC) progression or monoclonal component (M spike) progression by serum protein electrophoresis (SPE) or both. ClinREL could precede, be concurrent with or follow tumor marker elevation. Methods: We studied EBP and clinREL in 221 consecutive AHCT recipients for MM between 2005 and 2010. Patients with IIM and measurable M spike and SFLC elevation at diagnosis were analyzed. Patients were uniformly monitored at a single institution with SFLC and SPE every 8–12 weeks. Biochemical progression and clinREL were defined by standard IMWG criteria (Durie el al, Leukemia 2006). ClinREL was defined by new/progressive bone lesion or plasmacytoma, hypercalcemia (>11.5 mg/dl), decrease in hemoglobin ≥ 2 g/dl, rise in creatinine ≥ 2 mg/dl, or indication for new myeloma therapy. Results: 76 patients had clinREL after AHCT, 24 were excluded due to light chain predominant or oligosecretory disease, subsequent AlloHCT or other preemptive treatment. Among 52 evaluable patients, median age was 57 years (42–74), 72% had DSS stage III, 40% ISS stage III, 40% high-risk (HR) MM based on t(4;14), t(14;16), 17q del or karyotypic 13 q abnormality. Median time from AHCT to relapse was 484 days (76–1631). Three temporal patterns of MM recurrence were identified: EBP where SFLC/M spike elevation (or both) preceded clinREL (n=28, 54%); concurrent clinREL and SFLC/M spike elevation (n=22, 42%) or isolated clinREL (4%). The proportion of HR MM was similar among groups. The EBP cohort had superior OS compared to concurrent relapse cohort (log rank p Additionally in the EBP cohort, SFLC elevation alone (39%), M spike progression alone (22%) or concurrent SFLC and M spike (39%) progression could be the initial relapse marker. After isolated SFLC progression, median time to M spike progression was 112 days and to clinREL was 200 days. After isolated M spike progression median time to clinREL was 254 days. After simultaneous SFLC and M spike progression median time to clinREL was 234 days. In these 3 groups, overall time to clinREL after AHCT was longest for patients with M spike progression alone (17.8, 20.5 and 36.8 months, respectively; p=0.05). This was due to HR MM being more common in the first 2 groups (45% for isolated SFLC and 37% in the simultaneous SFLC/M spike group). Discussion: In this cohort of relapsed MM after transplant, 54% had isolated early biochemical progression prior to clinREL and this pattern predicted for superior survival. The category of clinREL may not be detected in advance in about one half of patients and predicts for more aggressive relapse. Present guidelines do not recommend SFLC monitoring for relapse in IIM patients with measurable serum M spike. Based on the above data early SFLC progression was seen in 20% of relapses and identified a higher risk subgroup within those with biochemical progression preceding clinREL. Disclosures: No relevant conflicts of interest to declare.

Pemetrexed is an antifolate chemotherapy agent that is active in malignant mesothelioma and non-small cell lung cancer (NSCLC). Pneumonitis is a rare side effect of Pemetrexed. We report the case of 72-year-old female with metastatic poorly differentiated lung adenocarcinoma. She was placed on maintenance pemetrexed and developed gradual progressive dyspnea after first cycle of maintenance of pemextrexed. The computed tomography (CT) of the chest showed ground glass opacity in both lung fields. Transbronchial lung biopsy showed uniform interstitial widening by a cellular chronic infiltrate with areas of type II pneumocyte and exudation of pale eosinophilic edema fluid, features consistent with acute lung injury. Patient improved both clinically and radiological after stopping pemetrexed and starting prednisone. Although pemetrexed induced lung injury is relatively rare, with the increasing use of pemetrexed in first-line treatment and in maintenance therapy of non-small cell lung cancer, awareness of this potential adverse effects is important.

Abstract 1301 Introduction: Allogeneic transplantation in MM is pursued in the hope of establishing an immune mediated graft vs. MM effect (allogeneic effect) in order to prevent relapse. After RIC allogeneic transplantation, donor immune function (donor chimerism) is established over time in the recipient. Long term B lymphocyte recovery may be delayed by graft vs. host disease (GVHD). GVHD may also be associated with the beneficial graft vs. MM effect. The recovery pattern of the original light chain associated with MM clone (involved free light chain) and the alternate light chain (uninvolved in MM and donor derived after allotransplant) serve as markers for MM progression vs. establishment of donor derived B cell function respectively after allotransplant. The serum FLC assay is a marker for both the progression of the recipient's original MM clone (rising involved FLC) as well as establishment of donor derived immune recovery (restoration of uninvolved FLC to normal).We hypothesized that the FLC assay is influenced by the competing effects of progression of the MM clone vs. the beneficial impact of alloimmunity/GVHD on relapse. Methods: Forty seven RIC allogeneic peripheral blood hematopoietic stem cell transplant recipients (45 matched sibling donors) for MM at the Medical College of Wisconsin (2005-2009) were studied. Conditioning regimen was,(200 cGY TBI +/− fludarabine). Median follow up was 2 years. Baseline and follow-up serum free light chain assay results at 3 monthly intervals were correlated with outcomes. The light chain associated with MM clone was designated as “involved” (IFLC) and the complementary light chain designated as the “uninvolved” (UFLC). Results: Overall (OS) and progression free (PFS) survival of cohort at 4.5 years was 54% (CI 36 – 72%) and 38% (CI 15– 61%) respectively. Treatment related mortality was 14.5%. All patients, except those with rapidly progressive MM (group 1 below), had suppression of both IFLC and UFLC immediately after RIC. Based on pattern of recovery of UFLC we identified 3 distinct groups. Group 1(n=12) – those who did not have any UFLC recovery, Group 2(n=10) those UFLC returned to normal levels within 6 months of RIC (early recovery) and a group 3 (n=25) where the UFLC recovery was delayed beyond 6 months (late recovery). Outcomes for all the three groups are shown in the table 1. The incidence of clinical GVHD was similar across the groups. Median PFS was significantly superior in the late recovery group (not reached at 5 years, vs. 4.6 mo and 11.8 mo in the other groups) (p=0.0001). In order to eliminate “survival by response” bias, we performed a landmark analysis, restricting the analysis to those alive at 6 mo after RIC and confirmed these findings (Fig 1.). Conclusion: Our data suggest that after RIC, with immunosuppressive conditioning, late recovery of UFLC is a marker of the efficacy of the allogeneic effect. The antineoplastic effect of donor alloimmunity likely explains the delayed recovery of UFLC (mediated by clinical/subclinical GVH activity) and paradoxically, better anti-MM effect in the late UFLC recovery group. Rapid progression of MM clone and non-establishment of a donor anti-MM effect explains the rapid relapse in those with no UFLC recovery. In the early recovery group, a higher risk of relapse is likely mediated by the absence of an alloimmune effect sufficient enough to delay B cell recovery and also insufficient for beneficial graft vs. MM effect. Since GVHD rates were similar across groups, the beneficial “allo immune effect” is likely independent of clinical GVHD. The FLC assay may be a sensitive marker of donor B cell recovery after allotransplant and needs further validation as a measure of donor derived antineoplastic effect in MM and other malignancies. Disclosures: No relevant conflicts of interest to declare.

Abstract 1867 Poster Board I-892 Bortezomib has been shown to have significant activity in the suppression of light chain production and induction of responses in patients with relapsed refractory AL Amyloidosis. We analyzed the outcomes of 16 (9 male) newly diagnosed biopsy proven AL Amyloidosis patients treated with Bortezomib based regimens at our institution. All patients received initial therapy with Bortezomib and dexamethasone (dex). Patients with a Karnofsky performance score ( KPS) >70 received Bortezomib at starting doses of 1.3 mg/m2 along with dexamethasone 40 mg on days 1,4,8, 11 ( with a 10 day rest period). Patients with a lower KPS received Bortezomib/Dex on a weekly schedule as tolerated. Dose adjustments were made based on side effects such as neuropathy, hypotension, GI disturbances or electrolyte imbalances. Patients tolerating Bortezomib/dex with improvement in KPS had cyclophosphamide (4) or lenalidomide (1) added to their initial therapy. Patients: Median age was 64 years (39–88). Nine had kappa light chain involvement. Organ involvement was renal (73%), cardiac (63%), hepatic (25%), tongue or soft tissue (20%), GI (30%). Median KPS was 70 (50 –100). Ten of the 16 patients were treated as in-patients due to multi-organ dysfunction. Five patients required hemodialysis within a month of diagnosis. Cardiac involvement was stage 3 (Mayo risk group) in 25%. Three patients were unevaluable: 2 dying before 2 cycles and 1 discontinued therapy (Grade 3 liver dysfunction). Median follow up was 5 months (range 2–33 mo). Results: Evaluable (receiving at least 2 cycles) patients have all had a free light chain response. The overall hematological response rate was 100% with 55% partial remission (PR) and 45% complete remission (CR). Median cycles to achievement of a light chain response was 2 (range 1–4). Four patients underwent autologous stem cell transplantation with no mortality. Five (40%) of the responders have had an organ response (3 renal, 1 macroglossia, 1 cardiac) with only patients alive for >5 months having any evidence of organ response. Five (40%) of the evaluable patients have died with progressive cardiac involvement (2), relapsed disease (2) or renal failure (1) with refusal of dialysis. In patients receiving at least one dose of bortezomib, non-hematologic toxicity (>grade 2) included -neuropathy (20%), hypotension (20%), severe diarrhea (12%), sepsis (12%), paralytic ileus (6%), liver dysfunction (6%), sudden death (6%). Conclusions: Bortezomib in combination with dexamethasone has a high response rate in newly diagnosed AL amyloidosis. This regimen was well tolerated in a cohort of severe, multisystem amyloidosis patients with low treatment related mortality. Light chain responses were fast whereas organ responses were not seen prior to 5 months of therapy. The regimen also served as a platform for further intensification with the addition of lenalidomide, cyclophosphamide or autologous transplant in responders. Disclosures: Off Label Use: Bortezomib for the therapy of amyloidosis. Hari:Millenium: Honoraria, Research Funding.

Bismuth and antimony-based chalcogenides have been extensively publicized in recent years owing to their intrinsic characteristics and inherent topological character. Such a system contains Bi2Se3, Bi2Te3, Sb2Te3, etc. The single crystalline facets of these samples were discovered to have a generation of ~2 THz while having a giant magneto-resistance of around ~300%. These inherent and dynamical features of the system make it resilient for several applications in optoelectronics and spintronics. The temperature-dependent assessment of conductivity, terahertz generation, and charge carrier dynamics aids in understanding the fundamental phenomena in the carrier mechanism of the chalcogenides. This chapter contains the essential fundamental knowledge of the single crystal chalcogenides via charge carrier & phonon dynamics and their response in the terahertz frequency domain.