The quasi-continuous, frequency-doubled Nd:Y AG (532 nm) laser safely and effectively treats freckles and lentigines in Fitzpatrick skin type IV.

Background Since the first case of coronavirus disease-19 (COVID-19) in Pakistan was reported in February 2020, the medical and paramedical staff has been working on the frontlines to deal with this disease. They have been facing significant strain and stress due to the pandemic, affecting their social, mental, and personal life. The purpose of this study is to investigate the psychological effects of the COVID-19 pandemic, etiology, personal coping mechanisms, and the strategies that are being adopted to reduce stress by the healthcare workers (HCWs) working in COVID-19 dedicated wards (group 2) and compare it with staff working in other departments but not in COVID-19 wards amid this pandemic (group 1) in various hospitals of Lahore, Pakistan. Methods The comparative cross-sectional study was designed which included doctors, nurses, and allied health professionals from various hospitals of Lahore, Pakistan. A questionnaire was designed which consisted of five sections, and 51 questions. A Chi-square test was used to compare the responses between these two groups. Results The study questionnaire was submitted by 200 participants, 100 responses for each group (see the Appendix). In group 1, HCWs not working in COVID-19 dedicated floors were afraid of getting infected, transmitting the infection to their families and concerned about using personal protective equipment (PPE) improperly. They reported a lack of concentration and tense muscles. The coping mechanisms of this group were exercise, strict precautions at work, and social distancing measures. While HCWs serving in COVID-19 dedicated wards were concerned and afraid of putting their families at risk by working in the high-risk environment; the major stresses in this group were: lack of knowledge about proper strategies for treatment, they faced insecurity due to physical and verbal violence by caretakers of COVID-19 patients, and lack of concentration. The coping mechanism was the support of their families and taking strict precautions, with self-isolation if required, to avoid any disease transmission to their families. The proposed strategies to be implemented included teaching skills for self-rescue as well as the implementation of policies at the administrative level to reduce working hours and frequent shift rotation. Conclusion The COVID-19 outbreak posed a great deal of mental stress among HCWs working on the COVID-19 floor as well as those serving in other departments of the hospital. The HCWs from group 1 were most afraid of getting infected and putting family members at risk, experienced tense muscles and lack of concentration, coped their stress by exercise and being more vigilant, and suggested the strategies of teaching skills for self-rescue and better community awareness. While the staff from the second group were most afraid of being the source of infection and violence from the caretakers of patients, experienced tense muscles, used family support, and strict isolation measures as coping mechanisms and suggested the strategies of selfrescue ...

Introduction: The impact of direct-acting antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial and a part of the scientific community believes it as a biased interpretation of data. Many studies have reported an aggressive pattern of HCC after DAA use. In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs or PI (PEG, pegylated-interferon). Methods: A total of 37 HCC patients after DAA treatment and 21 HCC patients after PI treatment were included. The diagnosis of HCC was made and information about demographics, HCC infiltrative pattern, portal vein thrombosis (PVT), time at initial presentation, Child-Turcotte-Pugh (CTP) score, and Barcelona Clinic Liver Cancer (BCLC) stage were compared in the two groups. Results: The total number of male patients in the DAA group was 62% while either gender was almost equal in PI. The age group of 40-60 was more prevalent in the DAA group while the PI group comprised more patients who were above 60 years. Patients in the DAA group presented after 3.35 years on average while patients in the PI group presented after about seven years. Most of the patients presented with the CTP stage of A. That is true for both groups. For BCLC staging, most of the patients had stage C, which means multiple lesions. At the initial presentation, most of the patients presented with multifocal lesions. Conclusion: Our study found no significant difference in the initial presentation between both groups. However, HCC patients with prior DAA therapy presented early than those with PI therapy.

Background: Patients diagnosed with thalassemia major who are transfusion dependant, have iron accumulation leading to iron toxicity and severe impairment in organs like heart, liver and endocrine organs which are highly sensitive to iron toxicity. This makes iron chelation therapy imperative for these patients. Half of the deaths resulting from iron toxicity related complications are attributed to cardiac complications. Iron chelation therapies have not been completely successful to prevent iron toxicity related complications like arrhythmia, cardiomyopathy and heart failure. Higher doses of iron chelation therapies have been associated with various side effects. Studies have shown L-type calcium channel blocker might be able to reduce iron uptake by myocardium. The aim of this meta-analysis is to assess the efficacy and safety of amlodipine to reduce myocardial iron concentration (MIC). Methods: We used PICO framework to do a systematic literature search using four database PubMed, Cochrane, Embase, and Web of Science using keywords, "Thalassemia" AND "Amlodipine" from the inception till July 2020. The initial search showed 90 articles out of which, six randomized clinical trials (RCT) (N= 226) were selected after exclusion of case reports, case series, preclinical trials, review articles, meta-analysis, and trials not providing any information about preventing iron overload in patients with transfusion dependent thalassemia. We extracted the data for myocardial iron concentration (MIC), myocardial T2, ferritin, hepatic iron/liver iron concentration (LIC), liver T2, left ventricular ejection fraction, response rate and adverse effects. DerSimonian-Laird random effects model was used to derive mean differences along with their 95% confidence interval (CI) using comprehensive meta-analysis version 3.0. Results: In six RCT, 96 patients were tested in experimental group and 97 in control group. In five RCT total number of male participants were 45 in experimental group and 54 in control group. 33 patients had splenectomy in experimental group and 41 in control group. The age range was 8 years to 31 years. The myocardial T2 score increased in amlodipine group compared to standard chelation group with significant mean difference estimated to be -0.62 (95% CI: -0.95-0.29, p-value: <0.001) in favor of amlodipine in meta-analysis of the four trials (Fig 1.). Statistically significant reduction in myocardial iron was seen in two trials on adding amlodipine to standard chelation therapy (N=55) (Table 1.) (Khaled et al and Fernandes et al). Significant difference was reported in liver T2 score and LIC at the end of six months between amlodipine and control group by Khaled et al. But, there was no statistically significant mean difference in serum ferritin and in liver MRI T2 between amlodipine group and control group with mean difference of -1143 (95% CI: -2410 to 124, p-value = 0.07) and -0.06 (95% CI: -0.463 to 0.338, p-value = 0.76) in meta-analysis of four and two trials respectively (Fig 2. And Fig 3.). El-Haggar et al compared amlodipine with spirulina and statistically significant improvement in myocardial T2 and NT-proBNP level was seen in both groups. Spirulina group also showed significant reduction in serum ferritin, which showed spirulina could also help reduce iron overload. Only mild adverse effects were reported by trials (Table 2.). No cases of severe hypotension, palpitation or any other serious adverse effects were seen in the amlodipine group. Conclusion: This systematic review and meta-analysis suggests that addition of amlodipine 2.5-5 mg/day to standard chelation therapy with monitoring for potential adverse effects, could benefit patients with thalassemia major by reducing cardiac iron overload and thus improve survival and quality of life. Future studies are required to study the role of amlodipine in reducing iron overload in endocrine organs that also absorb iron through voltage-gated channels, particularly considering the close association of cardiac siderosis with endocrine complications and the correlation of pancreas and MICs. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: Selinexor, an exportin 1(XPO1) inhibitor has demonstrated anti-leukemia activity as a single agent, as well as in combination regimens for the treatment of acute myeloid leukemia (AML). This systematic review aims to explore the efficacy and safety of selinexor based regimens for the treatment of AML. Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane library, ClinicalTrials.gov, ASCO, and ASH meeting websites. The initial databases yielded 698 articles (last updated search until July 20, 2020). After excluding review articles, duplicates, and non-relevant articles, we included data from eight clinical trials (Table 1 and Table 2). Results: Among a total of 286 patients, 259 were evaluated. Selinexor was given as monotherapy to 81 patients and as combination regimens to 178 patients. The total newly diagnosed (ND) AML patients were 48 and relapsed refractory (RR) AML patients were 238. Garzon et al. did a phase I dose-escalation trial (n=81) with selinexor as a single agent in ND-AML and RR-AML patients with a median of three prior lines of therapy. The overall response rate (ORR) was 14%. The median overall survival (OS) was 2.7 months and median progression-free survival (PFS) was 1.7 months. 15% of the patients discontinued the treatment temporarily due to adverse events (AEs). Bhatnagar et al. (n=25) studied selinexor with decitabine, in phase I clinical trial, in ND and RR-AML patients. The ORR was 40% with higher ORR in ND-AML (80%) compared to RR-AML (30%). At a median follow-up of 21.8 months, the median PFS was 5.9 months (95% CI: 2.4-8.7) and median OS was also 5.9 months (95% CI: 3.9-10.4). The PFS was longer for patients who responded to therapy (11.8 months) as compared to those who did not respond to therapy (4.4 months). In phase I/II trial by Daver et al. (n=14) with selinexor and sorafenib in RR-AML patients, the composite complete remission including CR, CR with incomplete blood count recovery (Cri), and CR with incomplete platelet recovery (CRp) was 35.7%. The event-free survival was 1.8 months (0.4-5.0) in FLT3-ITD Inhibitor failure cohort vs 2.1 months (0.7-2.1) in FLT3-ITD inhibitor naive cohort. A single-arm phase I study with selinexor, cytarabine, and daunorubicin was performed testing ND-AML patients by Sweet et al., (n=19). It showed an ORR of 53% and a median OS of 10.3 months (95% CI: 3.74-NR). The early death rate (death ≤ 60 days) was 4.8%. The phase I dose-escalation trial by Weng et al. (n=28) in ND and RR-AML patients with selinexor+cytarabine+mitoxantrone had a better response rate. The ORR was 64% with a higher ORR in ND-AML (87%) compared to RR-AML (38%). The phase I trial by Alexander et al. (n=18) with selinexor+ cytarabine+ fludarabine on RR-AML patients achieved an ORR of 60 % and CR of 33.3%. Fielder et al. (n=38) did a phase II clinical trial on RR-AML patients with selinexor+ cytarabine + idarubicin with 40 mg/m2 selinexor in one cohort (C1) and flat 60 mg dose of selinexor in the second cohort (C2). In C1 37% of patients and C2 40% of patients had previous stem cell transplantation (SCT). The ORR was almost the same in both cohorts, with 55 % in C1 vs 54.5% in C2. The phase I/II trial on RR-AML patients by Abboud et al. (n=40) with selinexor+ cladribine+cytarabine+filgrastim had a total of CR and CRi in 45% of patients with a median overall survival of 7.8 months (95%CI: 5.7-14.1) and median event-free survival of 6.1 months (95% CI: 4.5 - 7.8 months). The main hematological adverse events were pancytopenia and non-hematological adverse events were hypophosphatemia, hyponatremia, gastrointestinal disturbances, and fatigue (Table 2). Conclusion: Selinexor in combination regimens showed superior response rates compared to selinexor alone for the treatment of AML patients. The response rates were better in selinexor based three and four-drug regimens. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Background: Post-transplant lymphoproliferative disease (PTLD), a group of lymphoid disorders ranging from indolent polyclonal proliferation to aggressive lymphomas is a known complication following solid organ transplantation. The aim is to study the characteristics, predictive factors, management, and outcomes of PTLD among pediatric groups after liver transplantation in particular. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. Initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found five retrospectives observational, one observational cohort study, and one multicenter cohort in the pediatric population. We extracted the data for baseline characteristics, the reason for transplantation, recipient & donor EBV status, immunosuppression used, type & stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, response to therapy, adverse effects of therapy and mortality. Results: We included seven retrospective observational studies with a total (n) number of 3116 post-liver transplant pediatric patients, out of which 135 (4.33%) patients who developed PTLD as a complication of transplantation were studied. The male to female ratio was 41: 55 with the gender of 6 patients unknown. In five studies, with 118 PTLD patients, 34 recipients and 24 donors were positive for EBV at the time of liver transplantation. In addition to EBV, CMV status of patients in 5 studies showed 11/25 (44%) PTLD patients positive for CMV at the time of transplant. Post-transplant immunosuppression was achieved among these seven cohorts with cyclosporine, tacrolimus, OKT3, mycophenolate mofetil, prednisone, and basiliximab. The diagnosis was made via biopsy, showing all histopathological types including early lesions 14/46 (30.4%), polymorphic 13/46 (28.3%), monomorphic 18/46 (39.1%), and classic Hodgkin's lymphoma PTLD 1/46 (2.1%). Diffuse large B-cell lymphoma was the most common subtype in 6/18 (33.3%) of samples with monomorphic PTLD. Hsu, et al. in their study showed a five-year survival rate of 33.3% for St. Jude's classification stage IV lymphoma compared to 88.9% for stage I-III. The median age for 36 patients from three studies at the diagnosis of PTLD was 39.6 months (range 24-48 months). The median duration from transplantation to the diagnosis of PTLD was 13.48 months (range 8-24 months) in 54 patients from four studies. PTLD treatment was achieved with a combination of reduction or withdrawal of the immunosuppressive drugs with antiviral prophylaxis, chemotherapy, irradiation & the use of monoclonal antibodies in a total of 57 PTLD patients for which post-transplant immunosuppression data was available. Study by Hsu, et al. reported that 5/16 (31.3%) patients had acute graft rejection and 2 had a chronic rejection in a group of 16 PTLD patients undergoing treatment for PTLD with a reduction in immunosuppressive therapy. The overall mortality in patients who developed PTLD was 15/54 (27.8%) in four of the studies. Conclusions: Pre-transplant EBV-naive status in patients was associated with a higher incidence of PTLD. Advanced stage (Stage IV) lymphoma was associated with poor survival outcomes. Monomorphic histopathology may be most commonly associated with PTLD post-liver transplant. The main approach for the treatment of PTLD is the reduction or complete withdrawal of immunosuppressive drugs, administration of antiviral drugs (ganciclovir/valganciclovir),and lymphoma treatment with chemotherapy or irradiation, and monoclonal antibody therapy such as rituximab. Management of PTLD with reduction or withdrawal of post-transplant immunosuppressive drugs in one cohort was associated with an increased risk of graft rejection. Thus immunosuppressive therapy maintaining a fine balance between the risk of graft rejection and risk of developing PTLD may be associated with better patient outcomes post-liver transplant. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Background: Post-transplant lymphoproliferative disease (PTLD), is one of the major complications after organ transplantation. The aim of this study is to study the incidence, various risk factors especially EBV status, histopathological types, management, and outcomes of PTLD following kidney transplantation in the pediatric groups. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. The initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found five retrospectives observational, one retrospective questionnaire survey, one prospective observational, and one prospective trial study. We extracted the data for baseline characteristics, the reason for transplantation, recipient & donor EBV status, immunosuppression used, type & stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, response to therapy, adverse effects of therapy and mortality. Results: We included eight studies with a total (n) number of 1713 post-kidney transplant pediatric patients, out of which 148 (8.63%) patients who developed PTLD as a complication of transplantation were studied(table 1). Among the 148 patients diagnosed with PTLD, 96 (64.86%) were males, 49 (33.1%) female participants and 3 (2.2%) were unknown. 34/148 (22.97%) PTLD recipients were EBV (+), 86 (58.1%) EBV (-) and 28 (18.9%) unknown at the time of transplant. EBV status for donors was known in only 2 studies, showing 7/99 (7.1%) to be EBV (+) at the time of transplant. Höcker et al. have shown that antiviral prophylaxis with ganciclovir/valganciclovir in the first year post-renal transplant reduces the risk of EBV viremia. Post-transplant immunosuppressive drugs included tacrolimus, mycophenolate mofetil, azathioprine, sirolimus, cyclosporine, IL-2R antagonist, methylprednisolone, basiliximab, daclizumab, anti-thymocyte globulin/anti-lymphocyte globulin, OKT3. In some cohorts, rituximab and antiviral prophylaxis with ganciclovir or valganciclovir were also used in some patients. The median time from transplant to the diagnosis of PTLD from five studies with 125 patients was 16 months (0.9m-186m). Longmore et al. reported a bimodal distribution curve, with 50% presenting with early PTLD, i.e. after a median duration of 313 days and 50% presenting late after a median duration of 8 years. The histopathological types of PTLD were diagnosed via biopsy samples, showing predominance with polymorphic type 48 (32.4%), followed by monomorphic type 45 (30.4%), early lesion 4 (2.7%), Kaposi like PTLD 1 (0.67%) and Hodgkin lymphoma 1 (0.67%). The histological testing results from two of the studies also showed that 18/19 (94.7%) of diagnosed PTLD samples were EBV positive. PTLD was managed with reduction or cessation of the immunosuppressive drugs, anti-CD20 antibodies, chemotherapy for lymphoma, and in some cases mTOR inhibitors, intravenous immunoglobulins, and surgical resection. Data from 5 studies show the mortality rate of 12/51 (23.5%) among PTLD groups. The survival rate from 2 studies was 100% among 17 PTLD patients and 1 study showed a 5-year survival rate of 85% among 92 PTLD patients. Cleper et al. in their study concluded that the type of PTLD might have a significant effect on the outcome, as ¾ (75%) deaths in the PTLD group were attributed to anaplastic T-cell type. Conclusions: Our analysis shows the EBV infection is closely associated with a higher risk of PTLD development. Recipients' EBV seronegativity and positive EBV status of the donor have been shown to increase post-transplant EBV infection risk which is associated with a higher risk of PTLD development. Furthermore, our study shows that PTLD may occur in less than a month to more than 15 years of renal transplant. The polymorphic type was the most common and Hodgkin lymphoma-type, the least commonly reported PTLD type. The main therapeutic approach is the reduction or cessation of immunosuppression. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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