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Introduction- Injuries are increasingly recognized as a global public health epidemic. Around the world, almost 16,000 people die every-day from all types of injuries. Injuries represent 12% of the global burden of disease, the third most important cause of overall mortality and the main cause of death among 1-40-year age groups. Methodology- This hospital based cross-sectional study was conducted among the road traffic accident patients admitted in trauma care center of Government Medical College and Hospital Nagpur. Result- Most common type of injury was abrasion in 91.45% followed by laceration in 79.61% of study subjects. Other common injuries were contusion, fracture, internal hemorrhage, crush injury and dislocation. Majority of the study subjects i.e. 67.11% had head injury. Conclusion- Head injury was the most common injury found in the study. Abrasion and laceration was also more commonly found in study subjects. Head injury was found more in non-users of personal protective devices which was statistically significant.

The Ponseti method has revolutionized clubfoot treatment. Though completely neglected clubfeet are now rare, partially or incompletely and improperly treated feet are not uncommon. Relapses after successful correction may occur due to non-compliance with bracing. In scarred soft tissues due to previous surgery, soft tissue distraction using external fixation helps achieve correction. The Ilizarov fixator permits us to follow the Ponseti protocol, using correction methods that may either be constrained or unconstrained by hinges. Applying force vectors perpendicular to the moment arm allows us to correct the еquinus without damaging the ankle joint. All of the above is possible when the talus is round. Full correction of the deformity is possible. However, longterm follow-up of these patients has revealed stiffness of the ankle setting and frequently with tibio-talar osteophytes anteriorly. They are probably a reaction to excessive pressure developed in the joint due to the tight soft tissues. Hence the author has now added a mild shortening of the tibia and fibula to reduce soft tissue tension, rather than resorting to further soft tissue releases through scarred tissues. This allows faster correction with the Ponseti-Ilizarov protocol and allows good ankle range of motion to persist.

SETTING: Nepal Mediciti Hospital, Bhainsepati, Lalitpur, NepalOBJECTIVES: To determine antimicrobial resistance patterns, and the number and proportion of multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) cases among all patients with Acinetobacter isolates between September 2018 and September 2019.DESIGN: This was a hospital laboratory-based, cross-sectional studyRESULTS: Acinetobacter spp. (n = 364) were more common in respiratory (n = 172, 47.3%) and invasive samples such as blood, body fluids (n = 95, 26.1%). Sensitivity to AWaRe (Access, Watch and Reserve) Group antibiotics (tigecycline, polymyxin B, colistin) remained high. MDR (resistance to at least three classes of antimicrobial agents) (n = 110, 30.2%) and XDR (MDR plus carbapenem) (n = 87, 23.9%) isolates were most common in the Watch Group of antibiotics and found in respectively 99 (31.0%) and 78 (24.5%) patients (n = 319). Infected patients were more likely to be aged >40 years (n = 196, 61.4%) or inpatients (n = 191, 59.9%); 76 (23.8%) patients had an unfavourable outcome, including death (n = 59, 18.5%).CONCLUSION: A significant proportion of MDR and XDR isolates was found; nearly one patient in five died. Robust hospital infection prevention and control measures (particularly for respiratory and invasive procedures) and routine surveillance are needed to reduce infections and decrease the mortality rate. Tigecycline, polymyxin B and colistin should be cautiously used only in MDR and XDR cases.

In biomedical applications, the nature of biomaterials is transferred from bio-inert to make the metallic biomaterials biodegradable and multifunctional such as antibacterial, anti-proliferation, and anti-cancer, to eliminate secondary operation for implant removal. In the human body, Cortical and Cancellous are the two most important types of bone. Cortical bone is also known as the compact bone due to its dense structure and provides mechanical strength to the bone, whereas cancellous is the internal porous supporting structure. For a material that mimics the bone scaffold and acts as biomaterials, it should be non-toxic, possess good mechanical strength, helps in tissue growth, bone regeneration, and controlled biodegradation rate without any adverse effect. Many metals (Ti, Si, stainless steels), polymers, and ceramics are conventionally used as replacement biomaterials for broken or infected bone (orthopedic implants), but due to their unsatisfactory results for a long time use such as toxic metal ions release and stress shielding leading to secondary surgeries. Recently, researchers are focussing on biodegradable materials that do not need to be explanted from the organism. This review highlights the recent advancement in biodegradable materials i.e., magnesium, zinc, and iron, their manufacturing technique, challenges with present biomaterials, and some improvements that can help resolve the problems with current biomaterials.

BACKGROUND Congenital posteromedial bowing of tibia (CPMBT), a rare anomaly, is characterized by a decreasing deformity and a gradually increasing limb shortening. Lengthening in CPMBT has not been studied extensively. Our series compares the duration and complications of lengthening in younger versus older children to determine early lengthening safety and benefits. METHODS We studied 28 tibial lengthenings performed by a single surgeon in 23 patients, divided into 2 equal groups of 14 segments: group A 5 years or younger (preschool) and group B above 5 years. All were lengthened with circular external fixators, of which 3 were lengthened over a nail. We measured preoperative (bo) and postoperative (po) sagittal, coronal, and oblique plane deformities, initial limb length discrepancy (LLD), percentage LLD (% LLD), amount of lengthening (AmtL), percentage lengthening (%L), external fixator duration (EFD), and external fixator index (EFI). We graded complications by Lascombes' criteria, results by Association for the Study and Application of the Methods of Ilizarov bone score. RESULTS The mean age was 8.8±7.1 years; the mean follow-up was 7.9 years. Group A had significantly greater bo-sagittal, coronal, and oblique plane deformities. Mean LLD (3.4 cm in group A vs. 4.1 cm in group B) was similar in both. Expected LLD at maturity (LLDM) using the multiplier method was greater than previously reported (mean, range in group A: 7.2 cm, 4.4 to 9.5 cm; group B: 5 cm, 2.5 to 9.7 cm). Though AmtL (3.5 and 4.1 cm) was similar in both, %L was 24% in group A and 15.7% in group B (P=0.002). EFD (116.6 days) and EFI (33.7 days/cm) were lesser in group A compared with group B (200.3 days, P=0.001; 50.2 days/cm, P=0.01). Lascombes' triple contract was fulfilled in 11/14 lengthenings in group A versus 3/14 in group B. Association for the Study and Application of the Methods of Ilizarov bone score was good and excellent in both groups (P=0.44). CONCLUSIONS In a large series of lengthenings in CPMBT, we found younger children presenting with large deformities and large projected length discrepancies could be safely lengthened with significantly lesser EFD and complications than in older children. LEVEL OF EVIDENCE Level IV-therapeutic study.

Introduction: Prior to the introduction of tyrosine kinase inhibitors (TKIs), the presence of BCR-ABL1 conferred a poor prognosis in patients with acute lymphoblastic leukemia (ALL). We published in 2017 in Br J Haematology our analysis comparing the survival of Ph-Positive (Ph+) and Ph-negative ALL during the period when TKIs were universally available in the United States for Ph+ ALL using a Surveillance, Epidemiology, and End Results (SEER) Database analysis. Despite using TKIs, we have continued to remain reliant on cytotoxic chemotherapy regimens and allogeneic hematopoietic stem cell transplant (allo-HSCT) to achieve the best long-term outcomes. However, with the introduction of more potent TKIs and other novel agents, as well as better methods for monitoring minimal/measurable residual disease (MRD) the best approach is yet to be determined. In this study we present data from our institution with incorporation of TKIs in our modified USC ALL pediatric-based regimen without pegaspargase (PEG) (Table 1). Methods: This retrospective, single institution chart review included adults aged >18 with newly diagnosed Ph+ ALL between 2016 and 2020. Primary objectives were Overall survival (OS) and event-free survival (EFS) at 3 years for Ph+ ALL patients and secondary objectives were rates of complete remission/complete remission with incomplete recovery (CR/CRi), minimal residual disease (MRD) by flow cytometry and presence of BCR-ABL1 fusion transcript by real time polymerase chain reaction. Descriptive statistics of patients were reported and evaluated using Fisher's exact test. OS and EFS were reported through Kaplan Meier curves and Log-rank tests. Two-sided p value ≤0.05 was significant. RESULTS: 26 Ph+ ALL patients were identified. Median age at diagnosis was 42.5 years, with 42.3% males and 57.7% females. Median BMI was 31.1 kg/m 2, 42.3% had hepatic steatosis and 34.6% had CNS disease pre-induction. After induction 1, 91.3% of patients achieved CR/CRi, 8.7% were refractory, and 64.3% were MRD flow negative with 24% of patients with undetectable BCR-ABL1. After induction 2, 94.1% had achieved CR/CRi, 64.3% were MRD flow negative with 44.4% of patients with undetectable BCR-ABL1. After consolidation I, 78.6% were MRD flow negative. 50% of patients had received blinatumomab for MRD flow positivity early in the course and 34.6% underwent allo-HSCT. Of note, 65.4% of patients received Dasatinib only and 30.8% received at least 2 TKIs. Overall, 11.5% had known relapse, 12.5% died. 3-year OS was 83.3% and 3-year EFS was 86.6% (Table 2). When survival was stratified by transplant status, 3-year OS with allo-HSCT was 100% versus 70% without allo-HSCT (p=0.15) and 3-year EFS with allo-HSCT was 100% compared to 77.9% without allo-HSCT (Table 3). CONCLUSIONS: The use of the modified USC ALL regimen without PEG for the treatment of newly diagnosed Ph+ ALL combined with TKI at our institution led to an excellent 3-year OS (83.3%) and 3-year EFS (86.6%). All patients received TKI, half of the patients received blinatumomab and at least one third received allo-HSCT which likely led to higher OS even without PEG. We also observed a trend towards improved OS in recipients of allo-HSCT compared to patients who did not receive allo-HSCT (100% vs. 70%, p=0.15) although statistically not significant, it highlights the role of allo-HSCT in the management of Ph+ ALL patients. Figure 1 Figure 1. Disclosures Chaudhary: TCR2: Current equity holder in publicly-traded company; Celldex: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company; Pancella: Consultancy; Oncotartis: Consultancy; Athelas: Consultancy, Current holder of stock options in a privately-held company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy ; Allogene: Current equity holder in publicly-traded company. Douer: Adaptive: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Speakers Bureau; Jazz: Consultancy; Servier: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Yaghmour: Agios: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau; Astellas: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Jazz: Speakers Bureau.

Background: Haploidentical hematopoietic cell transplantation (haplo-HCT) has emerged as a popular alternative to traditional HLA-matched hematopoietic cell transplant. The major advancement of haplo-HCT has increased donor availability to many patients in need, therefore investigating the factors that may affect outcomes is necessary to improve overall survival and reduce transplant-related mortality. Data regarding optimal dose of CD34 cells, CD3 cells and CD34/CD3 ratio used during haplo-HCT to ensure favorable outcomes with post-transplant cyclophosphamide (PTCy) is lacking. Previously we have reported improved outcomes using CD34 cells limited to 7x10^6 cells/kg or less. In this report we are presenting an updated analysis including outcomes related to CD34/CD3 ratio used during haplo-HCT. Methods: We retrospectively analyzed adult patients at USC Norris Cancer Hospital who received haplo-HCT from 2014 to 2020. The primary endpoint assessed was 1-year GVHD-free/relapse-free survival (GRFS). Secondary endpoints included overall survival (OS), 1-year transplant related mortality (TRM) and incidence of acute and chronic GVHD. Kaplan Meier survival curves and log-rank tests were used to evaluate 1-year GRFS and OS with CD34 cell dose ≥ 7x10^6 cells/kg and < 7x10^6 cells/kg; CD3 cell dose < 2.5x10^8 cells/kg and ≥ 2.5x10^8 cells/kg; and CD34/CD3 ratio 3-5 and >5. Results: 103 adult haplo-HCT recipients were reviewed with 55.3% male and 44.7% female. The age range was 21-71 years old (median = 51), and a majority of patients were Hispanic (62%). The most common underlying hematologic disorders included AML (40.8%), ALL (34.1%), and MDS/MPN (13.6 %). 41.7% patients with leukemia were in CR1, 55% were CR2/CR3 and 78% were MRD negative by flow cytometry prior to transplant. 73% received myeloablative conditioning and 83.5% received peripheral blood stem cells. Median CD34 dose, CD3 dose and CD34/CD3 ratio were 6.1 x10^6cells/kg, 2.27 x10^8 cells/kg and 3.2 respectively. Median time to recovery of neutrophil, platelets, and lymphocyte was 17, 24, and 124 days respectively. Incidence of 1-year GRFS was 43.7%. 1-year TRM was 13.6% and rate of aGVHD and cGVHD was 42.7% (n = 44) and 35.9% (n = 37) respectively. There was no difference in 1-year GRFS and OS when multiple dose levels of CD34 cells and CD3 cells were compared. Although when dichotomized, a CD34 cell dose of ≥ 7x10^6 cells/kg compared to < 7x10^6 cells/kg showed higher dose had significant improvement in 1- year overall survival (p-value=0.01) but no statistical difference in 1 year GRFS (p value=0.24). CD3 cell dose < 2.5 x 10^8 cells/kg trended towards worse 1-Year GRFS compared to ≥ 2.5 x 10^8 cells/kg (43.9% compared to 58.6%; p-value 0.075), similarly CD3 dose of < 2.5x10^8 cells/kg showed a lower 1-year OS compared to > 2.5x10^8 cells/kg but was not statistically significant (78.7% compared to 89.4%; p-value 0.092). 1-year GRFS and OS did not show statistical difference at CD34:CD3 ratios of < 2, 2-3, 3-5 and > 5, although on cox regression analysis the HR for 1-year GRFS was 2.92 (95% CI 1.21-7.05) in patients with CD34:CD3 > 5 as compared to reference of < 2 (p-value 0.017). Multivariate regression also showed CD3 cell doses of 2-3x10^8 cells/kg and >3 x 10^8 cells/kg were associated with worse 1-year GRFS with HR of 0.43 and 0.40 and p-value of 0.041 and 0.048 respectively when compared to reference of < 1x10^8 CD3 cells/kg. Discussion: Our results demonstrate 43.7% survived 1 year compared with reports of 24-35%. The OS was significantly better in the CD34 dose > 7x10^6 cells/kg. CD3 2x10^8 cells/kg was associated with inferior 1-year GRFS. Conversely, higher CD34/CD3 ratio >5 was associated with increased 1-year GRFS. Thus, our findings indicate that along with improvement in OS by using >7x10^6 CD34 cells/kg, lower CD 3 cell dose 5 can improve 1-year GRFS in patients receiving haplo-HCT. Figure 1 Figure 1. Disclosures Chaudhary: Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy ; Athelas: Consultancy, Current holder of stock options in a privately-held company; Oncotartis: Consultancy; Pancella: Consultancy; Moderna: Current equity holder in publicly-traded company; Celldex: Current equity holder in publicly-traded company; TCR2: Current equity holder in publicly-traded company; Allogene: Current equity holder in publicly-traded company. Yaghmour: Jazz: Consultancy, Honoraria; Astellas: Consultancy; Takeda: Consultancy; Incyte: Consultancy.

The present investigation was carried out to study the refrigeration preservation of the cauda epididymal retrieved spermatozoa of buck in Tris egg yolk citrate (TEYC) dilutor containing pomegranate juice as antioxidant additive. The retrieved cauda epididymal spermatozoa extended in TEYC dilutor were studied in five groups by adding different concentration of pomegranate juice as additive (0% as control T1 group and 5%, 10%, 15% and 20% as treatment T2, T3, T4 and T5 groups, respectively) and storing at refrigerated temperature up to 48 hr. The results showed that the control extender had the least dead, abnormal and HOS non-reacted sperm percent among all treatments tested and that with increasing the pomegranate juice concentration in dilutor, the percentage of the dead, abnormal and HOST non-reacted spermatozoa increased significantly. The same trend was observed at all 12 hourly storage intervals indicating its detrimental effect on epididymal sperms of bucks at refrigeration temperature. The dead, abnormal, and HOST non-reacted sperm were significantly and positively interrelated with each other (r = 0.53-0.83). It was concluded that the inclusion of pomegranate juice in TEYC dilutor did not show any beneficial/antioxidant effect on epididymal sperms of buck in fresh or refrigerated semen and in fact all the levels of pomegranate juice (5% to 20%) were detrimental to cauda epididymal spermatozoa of a buck.

The study was carried out on the preservation of epididymal spermatozoa of buck at refrigerated temperature without and with tomato juice as a supplement in Tris egg yolk citrate extender. The eight pairs of testicles including epididymis (total 16) from slaughtered bucks were collected within 2–4 hours of their slaughter. Sperms collected from cauda epididymis were preserved at refrigerated temperature up to 48 hours in tris egg yolk citrate extender at 300 million sperm/mL with different concentration of tomato juice (0%, 4%, 6%, 8%, and 10%) and the physical characteristics of spermatozoa were assessed to know the effect of tomato juice (Tj). The mean dead, abnormal and HOST non-reacted spermatozoa increased significantly (p less than0.05) at every 12-hour intervals of preservation in the dilutor without and with different concentration of tomato juice. Tomato juice exerted an adverse effect on physical characteristics of sperm during refrigeration preservation. All the three sperm traits studied however revealed significant (p less thaN 0.01) positive interrelationships with correlations of 0.31 to 0.72.

Cytotoxicity assays are essential for the testing and development of novel immunotherapies for the treatment of cancer. We recently described a novel cytotoxicity assay, termed the Matador assay, which was based on marine luciferases and their engineered derivatives. In this study, we describe the development of a new cytotoxicity assay termed ‘Matador-Glo assay’ which takes advantage of a thermostable variant of Click Beetle Luciferase (Luc146-1H2). Matador-Glo assay utilizes Luc146-1H2 and D-luciferin as the luciferase-substrate pair for luminescence detection. The assay involves ectopic over-expression of Luc146-1H2 in the cytosol of target cells of interest. Upon damage to the membrane integrity, the Luc146-1H2 is either released from the dead and dying cells or its activity is preferentially measured in dead and dying cells. We demonstrate that this assay is simple, fast, specific, sensitive, cost-efficient, and not labor-intensive. We further demonstrate that the Matador-Glo assay can be combined with the marine luciferase-based Matador assay to develop a dual luciferase assay for cell death detection. Finally, we demonstrate that the Luc146-1H2 expressing target cells can also be used for in vivo bioluminescence imaging applications.

Fall Armyworm (FAW), Spodoptera frugiperda, is a polyphagous pest capable of feeding over 80 plant species and was indigenous to the Western Hemisphere. Within a span of 4 years, FAW has established itself throughout most of the regions in Africa and Asia causing significant losses in maize production. Owing to its revamped distribution range, it would be prudent to analyze the ensuing genetic changes and study the emerging phylogeographic patterns across the world. In this regard, we would like to provide a current snapshot of genetic diversity of FAW in India 2 years after the initial introduction and compare it with the worldwide diversity in order to trace the origins and evolutionary trajectories of FAW in India. We have investigated around 190 FAW samples from different regions in India for strain identity and polymorphism analysis on the basis of partial mitochondrial cytochrome oxidase I (COI) gene sequences. Apart from the ancestral rice and corn strain haplotype, our study demonstrates the presence of 14 more haplotypes unique to India at a haplotype diversity of 0.356. We were also able to record inter-strain hybrid haplotypes of rice and corn strains in India. Regional heterogeneity within Indian populations seems to be quite low representative of extensive migration of FAW within India. Distribution analysis of pairwise differences and rejection of neutrality tests suggest that the FAW population in India might be undergoing expansion. Our data is consistent with the findings suggesting a recent and common origin for invasive FAW populations in Asia and Africa, and does not indicate multiple introductions to India. This study reports the highest genetic diversity for Indian FAW populations to date and will be useful to track the subsequent evolution of FAW in India. The findings would have important ramifications for FAW behavior and composition throughout the world.

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization.

COVID-19, caused by SARS-CoV-2, continues to be a major health problem since its first description in Wuhan, China, in December 2019. Multiple drugs have been tried to date in the treatment of COVID-19. Critical to treatment of COVID-19 and advancing therapeutics is an appreciation of the multiple stages of this disease and the importance of timing for investigation and use of various agents. We considered articles related to COVID-19 indexed on PubMed published January 1, 2020-November 15, 2020, and considered papers on the medRxiv preprint server. We identified relevant stages of COVID-19 including three periods: pre-exposure, incubation, and detectable viral replication; and five phases: the viral symptom phase, the early inflammatory phase, the secondary infection phase, the multisystem inflammatory phase, and the tail phase. This common terminology should serve as a framework to guide when COVID-19 therapeutics being studied or currently in use is likely to provide benefit rather than harm. (AIDS Rev. 2021;22:40-47)

A cross-sectional study was conducted to investigate seroprevalence and virus prevalence of the H9 subtype of avian influenza virus in non-vaccinated broiler farms of dense poultry-populated districts, Lahore and Sheikhupura of Punjab-Pakistan. A convenient sampling method was adopted for collection of blood (n=500) and oropharyngeal swab (n=500) samples from 25 broiler farms of each district for hemagglutination inhibition assay and RT-PCR test, respectively. Proportional estimates were calculated using R software and overall seroprevalence of H9 was estimated at 36.3% (95% CI 33.3-39), with no significant difference (p>0.05) between Lahore (37.2 %, 95% CI=31.2-39.59) and Sheikhupura (35.4%, 95% CI= 29.64-39.76). RT-PCR identified 2% (4/200) pool level viral prevalence. None of the farms from Lahore districts were RT-PCR positive for H9. Simple logistic regression followed by multivariable analysis, identified the presence of foot bath/dipping area at the entrance (OR=0.7, 95% CI=0.52-0.93) and availability of rubber shoes for visitors (OR=0.36, 95% CI 0.26-0.48) as protective factors. History of respiratory signs (OR=1.51, 95%=CI 1.12-2.04), history of sudden death in past flocks (OR=3.26, 95% CI=2.41-4.41), and birds previously infected with avian influenza virus (OR=1.33, 95% CI=1-1.76) were significant risk factors. Negligence in preventive measures at farms level was associated with the spread of H9 infection between the farms. To control future outbreaks, biosecurity and continuous monitoring of non-vaccinated flocks are suggested.

Background:-The word “hernia” derived from Latin term meaning “a rupture”[1]. A hernia is defined as an area of weakness or complete disruption of fibromuscular tissue of body wall can pass through or herniate through defect[1]. In all ventral abdominal hernias, Inguinal hernia is the most common. Inguinal hernia repair is common in surgical practice. In past, the repair was pure open tissue repair which was changed to open prosthetic mesh repair. Laparoscopic groin hernia repair was first performed by Ger in 1979[1]. The laparoscopic approach to hernia repair has since evolved into common and effective procedure.Methods:-The presented study is a prospective, open labelled, randomized, comparative study during a period from May-2017 to March-2019. After taking written consent from the patients were randomly allocated to two groups. Group A, Open hernioplasty were operated with open tension free Lichtenstein’s hernioplasty. Group B, laparoscopic hernioplasty were operated with Transabdominal Preperitoneal(TAPP) repair. Those patients who fulfilled the inclusion criteria are included in study. The mode of presentation, surgical treatment and postoperative complications were all evaluated and compared.Results:-During the study there were no major life threatening complications were reported in either group. The postoperative pain and need of analgesics, presence of surgical site infections were more in Open hernioplasty group compared to laparoscopy group. The time taken for return to routine daily activities and work was earlier in patients treated with laparoscopy compared to open surgery and good cosmetic results.Conclusions:-Laparoscopic hernia repair has better, evolving & effective procedure in recent days compared to open hernia repair in terms of less postoperative complications, early recovery with good cosmetic results.

Aims Double-level lengthening, bone transport, and bifocal compression-distraction are commonly undertaken using Ilizarov or other fixators. We performed double-level fixator-assisted nailing, mainly for the correction of deformity and lengthening in the same segment, using a straight intramedullary nail to reduce the time in a fixator. Patients and Methods A total of 23 patients underwent this surgery, involving 27 segments (23 femora and four tibiae), over a period of ten years. The most common indication was polio in ten segments and rickets in eight; 20 nails were inserted retrograde and seven antegrade. A total of 15 lengthenings were performed in 11 femora and four tibiae, and 12 double-level corrections of deformity without lengthening were performed in the femur. The mean follow-up was 4.9 years (1.1 to 11.4). Four patients with polio had tibial lengthening with arthrodesis of the ankle. We compared the length of time in a fixator and the external fixation index (EFI) with a control group of 27 patients (27 segments) who had double-level procedures with external fixation. The groups were matched for the gain in length, age, and level of difficulty score. Results The mean gain in length was statistically similar in the two groups: 3.9 cm (1.5 to 9.0) in the study group and 4.2 cm (3.4 to 5.0) in the control group (p = 0.350). The mean time in a fixator was significantly less in the study group compared with the control group: 8.6 weeks (2.0 to 22.8) versus 30.2 weeks (25.0 to 35.4; p < 0.001). The mean EFI was significantly lower in the study group compared with the control group: 17.7 days/cm (10.6 to 35.6) versus 73.4 days/cm (44.5 to 102.3; p < 0.001). The ASAMI (Association for the Study and Application of the Method of Ilizarov) bone score was excellent in 22, good in four, and fair in one. The ASAMI functional score was excellent in 20 and good in seven. There were no infections, superficial or deep. Conclusion Double-level osteotomies or two procedures using a custom-made straight nail and external fixation can be used to correct deformities or to treat nonunion or malunion and may be combined with arthrodesis of the ankle with lengthening. It is a reasonably safe procedure that allows accurate and cost-effective treatment with a relatively short time in a fixator.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Primary effusion lymphoma (PEL) is a subtype of non-Hodgkin lymphoma associated with infection by Kaposi sarcoma-associated herpes virus (KSHV). PEL is an aggressive disease with extremely poor prognosis when treated with conventional chemotherapy. Narciclasine, a natural product present in Amaryllidaceae family of flowering plants including daffodils, belongs to a class of molecules termed ‘isocarbostyril alkaloid’. We have found that narciclasine displays preferential cytotoxicity towards PEL at low nanomolar concentrations and is approximately 10 and 100-fold more potent than its structural analogs lycoricidine and lycorine, respectively. Narciclasine arrested cell-cycle progression at the G1 phase and induced apoptosis in PEL, which is accompanied by activation of caspase-3/7, cleavage of PARP and increase in the surface expression of Annexin-V. Although narciclasine treatment resulted in a marked decrease in the expression of MYC and its direct target genes,time-course experiments revealed that MYC is not a direct target of narciclasine. Narciclasine treatment neither induces the expression of KSHV-RTA/ORF50 nor the production of infectious KSHV virions in PEL. Finally, narciclasine provides dramatic survival advantages to mice in two distinct mouse xenograft models of PEL. In conclusion, our results suggest that narciclasine could be a promising agent for the treatment of PEL.

Synthetic cannabinoids-associated coagulopathy cases are on the rise but are usually undetected in clinical settings due to less awareness among physicians and the lack of available literature on the subject. Patient may also not volunteer information about the use of such substances therefore detailed history is important. We present a case of a patient found to have coagulopathy of unclear cause as patient did not report the use of synthetic cannabinoid initially. J Med Cases. 2020;11(11):355-357 doi: https://doi.org/10.14740/jmc3561

Background: The use of post-transplant cyclophosphamide (PTCy)/tacrolimus/mycophenolate mofetil (MMF) for GVHD prophylaxis has improved outcomes in haploidentical hematopoietic cell transplantation (haplo-HCT). PTCy is now being evaluated in matched-related (MRD) and matched-unrelated (MUD) allo-HCT. Previous studies demonstrated improved GVHD-free/relapse-free survival (GRFS) when PTCy was combined with two immunosuppressive agents and PTCy has also been associated with better relapse-free survival (RFS) as demonstrated in De Jong et al 2019, though only one immunosuppressive agent was used. Currently, there is limited published data comparing outcomes using PTCy/tacrolimus/MMF to standard MRD/MUD GVHD prophylaxis of methotrexate (MTX)/tacrolimus. The importance of studying this comparison may help to improve GVHD outcomes in MRD and MUD allo-HCT. Methods: We retrospectively analyzed adult patients at USC Norris Cancer Hospital (age ≥ 19) who received allo-HCT from 2018 to 2020. The primary end-points assessed were incidence and severity of 1-year aGVHD and cGVHD. Secondary end-points included day+100 mortality, 1-year overall survival (OS), 1-year RFS, 1-year transplant-related mortality (TRM), and 1-year GRFS, defined as grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the 1-year post-HCT period. Results: A total of 65 adult MRD and MUD allo-HCT recipients and 53 haplo-HCT patients were reviewed. Of the MRD/MUD patients evaluated, approximately 51% (n = 33) were female and 49% (n = 32) were male. The age range was 20-69 years old (median = 46), and the most common diseases included ALL (46%), AML (31%), MDS (11%), and others (i.e. lymphoma, aplastic anemia (AA), myelofibrosis) (12%). 34% (n = 22) of patients received PTCy on D+3 and D+4 with tacrolimus/MMF/ on D+5 as GVHD prophylaxis and 66% (n = 43) of patients received MTX/tacrolimus on D+1, +3, +6, and +11 as GVHD prophylaxis. All haplo-HCT patients received standard PTCy/tacrolimus/MMF. Stem cell source was primarily PBSC except in HLH and AA patients. The PTCy group had more MUD allo-HCT (64%), degree of antigen mismatch (56%), and median age of 50.5 years compared with the MTX group at 44%, 47%, and 44 years respectively. 70% in the MTX group received MAC compared with 45% in the PTCy group. The haplo group had similar demographics to the MTX group. The mean CD34 cell doses in the PTCy, MTX, and haplo groups were 4.87, 5.36, and 7.24x106 cells/kg respectively. Incidences of total GVHD, aGVHD, and aGVHD grade 3 or 4 in the PTCy group were 55%, 50%, and 4.5% respectively compared with 65%, 35%, and 7% in the MTX group, though not significant. The haplo group had 68%, 55%, and 1.9% respectively. Incidence of total cGVHD and cGVHD requiring systemic therapy in the PTCy group was 4.5% and 0% respectively compared with 30% (p = .02) and 23% (p =.01). The haplo group had 13% and 1.9% respectively. Day+100 mortality, 1-year OS, 1-year RFS, 1-year TRM, and 1-year GRFS in the PTCy group were 0%, 80%, 60%, 0%, and 64% respectively compared with 7%, 88%, 90%, 7.3%, and 59%. The haplo group had 3.8%, 86%, 89%, 14%, and 66%. In a univariate analysis, factors significantly associated with GVHD were disease status (p = .0.12) and CD34 dose (p = 0.015) and antigen mismatch (p = 0.04) was associated with increased mortality. Discussion: Our results demonstrate improved overall and extensive cGVHD outcomes in the PTCy group and thus an improvement in 1-year GRFS. Furthermore, incidence and severity of 1-year cGVHD in this group are improved when compared with previously reported outcomes. 1-year GRFS reported in De Jong et al 2019 was 45% and 1-year GRFS reported for all groups in our study is higher at 66%, 64%, and 59% for the haplo, PTCy, and MTX groups respectively. Although this was not significant, it may be clinically meaningful given the significant improvement in extensive GVHD and improvement in all other secondary end-points except 1-year OS and RFS. Furthermore, the PTCy group had a higher percentage of mismatched antigens yet demonstrated superior outcomes. 1-year OS and RFS were superior in the MTX group however this is likely due to sample size differences. The improved extensive cGVHD and GRFS outcomes observed using PTCy/tacrolimus/MMF in the MRD/MUD setting should continue to be evaluated and currently there is an ongoing prospective, randomized study to further investigate. Disclosures Yaghmour: Jazz: Consultancy, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction: Takayasu’s disease (TD) (pulseless disease, aortic arch syndrome) is a rare but potentially life-threatening chronic giant cell vasculitis. The major complications attributed to the disease include Takayasu’s retinopathy, secondary hypertension, aortic regurgitation, and arterial aneurysm. The aim of this study is to describe a patient with Takayasu’s disease and scleritis and to show its association.Case report: We describe a 44-year-old female patient with Takayasu’s disease who presented with bilateral anterior scleritis in the form of painful red eye. Patient did not have any associated autoimmune diseases. Patient was diagnosed to have TD and was treated with immunosuppressant.Conclusion: Scleritis though rare can be a vasculitic feature of TD. This is a first report of Takayasu’s disease with scleritis, which has been documented in Nepal.

INTRODUCTION: Hispanic patients with acute lymphoblastic leukemia (ALL) are historically known to have poor outcomes compared to non-Hispanic patients. Our institution, LAC-USC (LA County Hospital/University of Southern California) has shown a complete remission rate of 96% with use of pegasparagase at 2000 IU/m2 using the USC ALL regimen (based on CCG-1882) for patients aged 17-55 years with a 7-year OS of 51% reported in 2014. The modified USC ALL regimen now uses a single dose of cytarabine rather than fractionated doses and uses a single dose 3g/m 2 methotrexate compared to 1g/m 2 (2.5g/m 2 if T-cell) D1, 15 in original USC ALL regimen to improve compliance, while consolidation was increased to six cycles allowing for PEG holidays to improve toxicity (Table 1). Since our institution takes care of a large population of Hispanic patients with ALL, we now report outcomes in Hispanic and Non-Hispanic patients using the modified USC ALL regimen in the era of novel agents like blinatumomab and inotuzumab. METHODS : This retrospective, single institution chart review included adults >18 years old with newly diagnosed Ph-negative ALL (2016-2020). Primary objectives were 3-year over-all survival (OS), event-free survival (EFS), disease-free survival (DFS). Secondary objectives were complete remission/complete remission with incomplete recovery (CR/CRi), minimal residual disease (MRD) by flow cytometry, descriptive statistics of patients who were stratified into Hispanic and non-Hispanic cohorts and evaluated using Fisher's exact test. OS, DFS, EFS were reported through Kaplan Meier curves and Log-rank tests. Two-sided p-value ≤0.05 was significant. RESULTS: 121 Ph-negative patients were reviewed. 87 were Hispanic patients (HP) and 34 non Hispanic patients (NHP). Median ages were 39 and 35 years (p=0.51) and median BMI were 29 and 26.9 kg/m 2 (p=0.42), respectively. There were about equal males and females in HP while NHP had 70.6% males compared to 29.4% females (p=0.076). Both HP and NHP were mainly of the Ph-negative ALL subtype, 50.6% vs 47.1%, followed by Ph-like, 25.4% vs 20.6%, respectively (p=0.884). Majority of the population were unfavorable risk by NCCN karyotypic risk stratification, 55.9% in HP compared to 56.0% in NHP (p=0.99). Over-all, no significant difference between baseline characteristics in both cohorts. After induction 1: CR/CRi was 85.9% in HP and 73.4% in NHP (p=0.09). MRD negativity by flow cytometry in HP was 41.4% compared to 26.4% in NHP (p=0.13). After induction 2: 83% of HP were in CR/CRi compared to 80% in NHP (p=0.99) and MRD negativity by flow was 35.6% in HP compared to 32.4% in NHP (p=0.73). Blinatumomab was given in 33.3% of HP and 32.3% of NHP (p=0.92) while only 5.7% of HP and 2.9% of NHP received inotuzumab (p=0.99). 34.5% of HP underwent allogenic hematopoietic stem cell transplant (allo-HSCT) versus 26.5% in NHP (p=0.40). 3-year OS was 92.2% in HP versus 67.4% in NHP (p=0.004). 3-year DFS was 92.8% in HP versus 60.7% in NHP (p=0.003). 3-year EFS was 54.1% in HP versus 32.3% in NHP (p=0.02) (Table 2). Rate of relapse for HP and NHP were 23.4% vs 29.4% (p=0.74) while rate of mortality for HP and NHP were 7.5% vs 28% (p=0.015), respectively. No clear difference in grade 3/4 PEG toxicities were found in HP and NHP except more hypertriglyceridemia in HP (p=0.019). CONCLUSIONS: We present comparison of outcomes in Hispanic and non-Hispanic patients using our modified USC ALL pediatric-based regimen in an era of novel agents. Our data shows significantly better outcomes in Hispanic patients compared to non-Hispanic patients [OS (92.2% vs 67.4%, p=0.004), DFS (92.8% vs 60.7%, p=0.003) and EFS (54.1% vs 32.3%, p=0.02)]. This study demonstrates that given equal access to care (eg. receiving blinatumomab, allo-HSCT), outcomes in HP with Ph-negative ALL are not worse, but rather superior to those in NHP. Utilization of novel immunotherapy like blinatumomab in the salvage setting to achieve deeper molecular response and increased utilization of haploidentical allo-HSCT have likely contributed to reducing ethnic disparities in Hispanic ALL patients. Future studies are needed to validate these findings with larger patient populations. Figure 1 Figure 1. Disclosures Chaudhary: Oncotartis: Consultancy; Pancella: Consultancy; Moderna: Current equity holder in publicly-traded company; Celldex: Current equity holder in publicly-traded company; TCR2: Current equity holder in publicly-traded company; Allogene: Current equity holder in publicly-traded company; Athelas: Consultancy, Current holder of stock options in a privately-held company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy . Douer: Jazz: Consultancy; Amgen: Consultancy, Speakers Bureau; Adaptive: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Speakers Bureau; Servier: Consultancy, Speakers Bureau. Yaghmour: Takeda: Consultancy, Speakers Bureau; Astellas: Speakers Bureau; Alexion: Speakers Bureau; BMS: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Jazz: Speakers Bureau.

Intro: Acute and chronic graft versus host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplant (allo-HSCT). Post-transplant cyclophosphamide (PTCy), alongside mycophenolate mofetil (MMF) and tacrolimus (TAC), is known to be effective in reducing cGVHD in haploidentical (HI) transplant recipients. Results of the prospective randomized HOVON-96 trial in recipients of matched related (MRD) and unrelated donors (MUD) showed that PTCy leads to a reduction in risk of severe cGVHD. However, the role of PTCy in HSCT with acute lymphoblastic leukemia (ALL) remains controversial. The purpose of this study is to evaluate outcomes using PTCy, TAC, and MMF for GVHD prophylaxis in MRD and MUD stem cell recipients who have ALL. Methods: This study is a retrospective analysis of adult patients (aged 19 and up) with ALL who received MRD, MUD, and HI HSCT at USC Norris Cancer Hospital from 2018 to 2020. The primary end-points were to compare incidence of aGVHD and cGVHD within the first year post-transplant after receiving MRD, MUD, and HI donor transplants. Secondary end-points were day +100 mortality, 1-year overall survival (OS), relapse free survival (RFS), transplant-related mortality (TRM), and GRFS within the same subgroups. Kaplan-Meier curves and Log Rank tests were used to evaluate a difference in outcomes. Results: A total of 46 patients with ALL who received HSCTs were identified and separated based on type of GVHD prophylaxis received: 7 (15.1%), 16 (34.8%), and 23 (50.0%) in the PT-Cy, HI and standard groups respectively. Demographic data can be found on Table 1 attached. Baseline characteristics among all groups were similar with the exception of the more Human Leukocyte Antigen (HLA) mismatch (p Discussion: In this single institution analysis, we observed that patients with ALL who underwent HI transplant had the best outcomes. Moreover, patients receiving MUD/MRD HSCT with use of PTCy had a non-significant reduced incidence of aGVHD and cGVHD, though had significantly worse 1-year OS, RFS, and GRFS when compared to standard GVHD prophylaxis or patients receiving HI transplants. We believe this is likely a multifactorial process. However, the increased percentage of mismatched antigens in the MUD transplants (p=0.19) and higher proportion of patients receiving less than 5.0 x 10^6 CD34+ cells/kg (p=0.02) in the PTCy group is important to acknowledge and can also be contributing to their poorer outcomes. We pose the idea that the use of PTCy may also lead to a reduced graft vs. leukemia effect in this population and thus a higher incidence of relapse and worse outcomes overall. A larger, prospective study should be considered to take into account these factors to better determine if patients with ALL could benefit from PTCy for GVHD prophylaxis. Figure 1 Figure 1. Disclosures Chaudhary: Celldex: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company; Pancella: Consultancy; Oncotartis: Consultancy; Athelas: Consultancy, Current holder of stock options in a privately-held company; TCR2: Current equity holder in publicly-traded company; Allogene: Current equity holder in publicly-traded company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy . Yaghmour: Takeda: Consultancy, Speakers Bureau; Astellas: Speakers Bureau; Alexion: Speakers Bureau; BMS: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Jazz: Speakers Bureau.

INTRODUCTION: The use of pediatric inspired regimens in adolescent young adults and adults has improved outcomes in acute lymphoblastic leukemia (ALL). CALGB 10403 was prospectively tested in patients 17-39 years, showing a 3-year event free survival of 59%. In 2007, our institution reported outcomes after incorporating peg-asparaginase (PEG) dosed at 2000mg/m 2 in induction for patients aged 17- 55 years. This regimen was well tolerated and resulted in a complete remission (CR) rate of 96%. In 2014, we reported experience with the use of multiple doses of PEG (CCG-1882) for newly diagnosed ALL adult patients, with a 7-year overall survival (OS) of 51%. Since our last report, the USC ALL regimen consisting of 2 induction phases, has been further modified with a goal of maintaining good outcomes, and improving compliance and toxicities. Fractionated doses of cytarabine were changed to a single dose, the methotrexate dose of 1g/m 2 (2.5 g/m 2 if T-cell) given D1,15 of intensification phases was changed to 3g/m 2 (B and T cell) given in single doses, and consolidation was increased to six cycles allowing for PEG holidays (Table 1). Moreover, the approval and incorporation of novel agents such as blinatumomab and inotuzumab also changed outcomes in ALL. Therefore, this study reports an update of outcomes since further modification of the USC ALL pediatric-based regimen in the era of novel agents. METHODS: This is a retrospective review which included adults aged >18 with newly diagnosed Philadelphia negative ALL between 2016 and 2020 treated at USC/Norris Cancer Center and Los Angeles County Hospital (LAC). Primary objectives were over-all survival (OS), event-free survival (EFS), disease-free survival (DFS) at 3 years, and secondary outcomes were complete remission/complete remission with incomplete recovery (CR/CRi) rates and minimal residual disease (MRD) by flow cytometry. OS, DFS, EFS were reported through Kaplan Meier curves and Log-rank tests. Two-sided p value ≤0.05 was significant. RESULTS: 121 patients with Ph-negative ALL were identified (49.6% Ph-negative B-ALL, 24% Ph-like B-ALL, 0.8% B cell lymphoblastic leukemia (LBL), 9.1% T cell ALL, 4.1% T cell LBL, 4.1% early T-cell, 5.8% mixed phenotype acute leukemia (MPAL). Median age at diagnosis was 38.5 years and maximum age of patient to receive pegasparagase during induction 1 was 63 years. 71.9% Hispanic, 15.7% white, 9.9% Asian, 2.5% African American. 57.9% males, 42.1% females. 3.4% were favorable, 4.2% intermediate, 54.6% unfavorable and 37.8% unknown by karyotypic risk stratification. Median BMI was 28.9 kg/m 2.54.6% had hepatic steatosis either on history or imaging and 5.1% had CNS disease pre-induction. Post-induction 1, 81.4% of patients achieved CR/CRi and 50% MRD negative. Post induction 2, 82.2% achieved CR/CRi, 67.7% MRD flow negative. Post-consolidation 1, 90.9% were MRD flow negative. 33.1% subsequently received blinatumomab for MRD positive disease, 5% given inotuzumab for relapsed disease, 32.2% underwent allogenic hematopoietic stem cell transplant (allo-HSCT). Median number of pegasparagase doses received during treatment was 2, rate of relapse and mortality was 27.3% and 13% respectively. Median OS and DFS were not reached but median EFS was 35 months. 3-year OS was 85.3%, when stratified according to MRD post induction 2; 3-year OS was 91.7% for MRD positive patients and 91.2% for MRD negative patients (p=0.55). 3-year DFS was 83.2%; 88.2% for MRD positive patients and 97.4% for MRD negative patients (p=0.22). 3-year EFS was 47.3%; 51.3% for MRD positive patients and 50.6% for MRD negative patients (p=0.49) (Tables 2-3). Use of pegasparagase resulted in grade 3/4 toxicities including hypersensitivity (4.1%), transaminitis (21.5%), pancreatitis (5.4%), hypertriglyceridemia (49.5%), hypofibrinogenemia (45.5%), hyperbilirubinemia (21.5%) and thrombosis (16.5%). CONCLUSIONS: Pediatric-based modified USC ALL induction regimen led to a high 3-year OS (85.3%), DFS (83.2%) and EFS (47.3%) with predictable toxicity and compares favorably with original USC ALL regimen, CALGB 10407, GRAALL 2005 and USC/MSKCC regimen. Interestingly, MRD positivity after induction 2 did not adversely affect OS, DFS or EFS, which is likely due to incorporation of blinatumomab and inotuzumab. These agents could have allowed for deeper remissions allowing Ph-negative patients with residual disease to receive allo-HSCT. Figure 1 Figure 1. Disclosures Chaudhary: Oncotartis: Consultancy; Pancella: Consultancy; Moderna: Current equity holder in publicly-traded company; Celldex: Current equity holder in publicly-traded company; TCR2: Current equity holder in publicly-traded company; Allogene: Current equity holder in publicly-traded company; Athelas: Consultancy, Current holder of stock options in a privately-held company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy . Douer: Servier: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Adaptive: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Speakers Bureau; Jazz: Consultancy. Yaghmour: Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau; Astellas: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Jazz: Speakers Bureau; Agios: Consultancy, Speakers Bureau.

Infected nonunions of tibia pose many challenges to the treating surgeon and the patient. Challenges include recalcitrant infection, complex deformities, sclerotic bone ends, large bone gaps, shortening, and joint stiffness. They are easy to diagnose and difficult to treat. The ASAMI classification helps decide treatment. The nonunion severity score proposed by Calori measures many parameters to give a prognosis. The infection severity score uses simple clinical signs to grade severity of infection. This determines number of surgeries and allows choice of hardware, either external or internal for definitive treatment. Co-morbid factors such as smoking, diabetes, nonsteroidal anti-inflammatory drug use, and hypovitaminosis D influence the choice and duration of treatment. Thorough debridement is the mainstay of treatment. Removal of all necrotic bone and soft tissue is needed. Care is exercised in shaping bone ends. Internal fixation can help achieve union if infection was mild. Severe infections need external fixation use in a second stage. Compression at nonunion site achieves union. It can be combined with a corticotomy lengthening at a distant site for equalization. Soft tissue deficit has to be covered by flaps, either local or microvascular. Bone gaps are best filled with the reliable technique of bone transport. Regenerate bone may be formed proximally, distally, or at both sites. Acute compression can fill bone gaps and may need a fibular resection. Gradual reduction of bone gap happens with bone transport, without need for fibulectomy. When bone ends dock, union may be achieved by vertical or horizontal compression. Biological stimulus from iliac crest bone grafts, bone marrow aspirate injections, and platelet concentrates hasten union. Bone graft substitutes add volume to graft and help fill defects. Addition of rh-BMP-7 may help in healing albeit at a much higher cost. Regeneration may need stimulation and augmentation. Induced membrane technique is an alternative to bone transport to fill gaps. It needs large amounts of bone graft from iliac crest or femoral canal. This is an expensive method physiologically and economically. Infection can resorb the graft and cause failure of treatment. It can be done in select cases after thorough eradication of infection. Patience and perseverance are needed for successful resolution of infection and achieving union.

Context Hematopoietic stem cell transplant (HSCT) recipients are generally considered high risk for poor outcomes following COVID-19 infection. The CIBMTR observational report published by Sharma et al. found that recipients of allogeneic HSCT who contracted COVID-19 had poor overall survival with a 30-day mortality of 32%. However, there are relatively few other studies that evaluate the effect of COVID-19 on HSCT recipients, especially in the setting of in vivo T-cell depletion protocol. Objective This is a single-institution, retrospective analysis evaluating outcomes of HSCT recipients who were diagnosed with COVID-19 between March 2020 and April 2021. Patients There were 21 patients at our institution who had undergone HSCT and subsequently contracted COVID-19. Their median age was 53 years at the time of diagnosis. Thirteen of the patients were Hispanic (61.9%). Six of the patients received match-related stem cells (28.6%), 7 received cells from match unrelated donors (33.3%), and 7 received cells from haploidentical donors (33.3%). Fifteen of the patients (71.4%) received myeloablative conditioning regimens, whereas 5 (23.8%) received reduced intensity or non-myeloablative regimens. One patient had received an autologous stem cell transplant. Our most common GVHD prophylaxis regimens were PTCy/Tacro/MMF (12 pts, 57.1%) and Tacro/MTX (6 pts, 28.5%). Results Our primary endpoint in this retrospective analysis was non-relapse mortality within 60 days of COVID-19 diagnosis. Of the 21 patients with confirmed COVID-19 infection, 1 passed away 20 days after diagnosis, giving us a 4.8% case fatality rate. The median time of COVID-19 diagnosis post-transplant was 469 days. Sixteen of the 21 patients were symptomatic at the time of diagnosis (76.2%). Eight patients received steroids for treatment of COVID-19 (38.1%). Seven of the 21 patients (33.3%) were hospitalized for a median of 7 days (range, 5–17 days), with 2 requiring ICU level of care (9.5%). One patient was intubated and ultimately passed away. Conclusion Our data suggest that our HSCT recipients who contracted COVID-19 have had generally good short-term outcomes. Longer follow-up is required to determine if a COVID-19 diagnosis has any effect on long-term transplant related complications and outcomes in this population.

Background: Cam femoroacetabular impingement is caused by a misshapen femoral head with a reduced head neck offset, commonly in the anterolateral quadrant. Friction in flexion, adduction and internal rotation causes limitation of the hip movements and pain progressively leading to labral and chondral damage and osteoarthritis. Surgical hip dislocation described by Ganz permits full exposure of the hip without damaging its blood supply. An osteochondroplasty removes the bump at the femoral head neck junction to recreate the offset for impingement free movement. Materials and Methods: Sixteen patients underwent surgery with surgical hip dislocation for the treatment of cam femoroacetabular impingement by open osteochondroplasty over last 6 years. Eight patients suffered from sequelae of avascular necrosis (AVN). Three had a painful dysplastic hip. Two had sequelae of Perthes disease. Three had combined cam and pincer impingement caused by retroversion of acetabulum. All patients were operated by the trochanteric flip osteotomy with attachments of gluteus medius and vastus lateralis, dissection was between the piriformis and gluteus minimus preserving the external rotators. Z-shaped capsular incision and dislocation of the hip was done in external rotation. Three cases also had subtrochanteric osteotomy. Two cases of AVN also had an intraarticular femoral head reshaping osteotomy. Results: Goals of treatment were achieved in all patients. No AVN was detected after a 6 month followup. There were no trochanteric nonunions. Hip range of motion improved in all and Harris hip score improved significantly in 15 of 16 cases. Mean alpha angle reduced from 86.13° (range 66 ° –108 ° ) to 46.35° (range 39 ° –58 ° ). Conclusion: Cam femoroacetabular Impingement causing pain and limitation of hip movements was treated by open osteochondroplasty after surgical hip dislocation. This reduced pain, improved hip motion and gave good to excellent results in the short term.

Herpes Zoster is produced by reactivation of latent varicella zoster from the dorsal root ganglion of sensory nerves. It is common in older individuals and rarely described in Pediatric age group. Its occurrence in younger age should be viewed with suspicion. We describe an 11-year-old Nepali child who presented with herpes zoster ophthalmicus of right half of the forehead and a perforated corneal ulcer in the right eye. On investigations he was found to have been infected with human immunodeficiency virus (HIV). Patient responded well to systemic acyclovir. Thus, herpes zoster ophthalmicus in a young child should be viewed with suspicion.

Background: HIV/AIDS has various ocular manifestations. Objective: To find out eye findings among HIV positive patients in the era of antiretroviral therapy. Method This Hospital based cross sectional descriptive study was carried at B. P. Koirala Lions Centre for Ophthalmic Studies. Patient profile, WHO clinical stage, CD4+ cell count, duration of HIV, antiretroviral therapy, and systemic diseases were recorded. All the cases underwent ocular examination as per the study protocol and the findings were noted in a proforma developed for the study. The results were analysed with SPSS 14.0. Results: Of 100 HIV positive cases (including 55 antiretroviral therapy patients) 62% patients were male and 38% were female. The mean age of presentation was 27.72 years. Heterosexual transmission (62%) was the commonest mode of transmission of HIV. Thirty seven percent patients were illiterate. Systemic disease was present in 20% cases. Ocular complaint was present in 53% patients. Ocular disease was present in 40% HIV positive patients. Almost 55% of these cases were on antiretroviral therapy. Moderate to lower CD4 count patient had frequent eye disease. Patients in WHO Stage III and IV also had frequent eye problems. Anterior segment and external ocular disorder was present in 25% patients. The commonest manifestation was conjunctivitis in10% of total cases. Posterior segment manifestation was present in 11%, neuro-ophthalmic lesion in 4% and orbital lesion in 1% patient. Conclusion: Anterior segment manifestation is still common ocular manifestations in HIV positive patients in Nepal. Patients in WHO Stage III and IV are more vulnerable for eye changes. Young aged male and migrant workers are at risk of acquiring HIV in developing country like Nepal. Eye findings even in patientson antiretroviral therapy are similar. However, large sample size and long follow up study is required to have final disclosure. Nepal J Ophthalmol 2016; 8(15): 62-70

Urinary tract infections are one of the most common causes of imaging in a typical radiology practice on a daily basis and are a great concern for the patient and referring physician. There is an overlap in imaging findings in some of the renal infections, but many urinary tract infections have characteristic imaging features. Patients with uncontrolled diabetes mellitus or immune compromised status are at high risk for urinary tract infection, and in these patients, symptoms often are subtle; hence, urgent imaging is required to rule out life-threatening complications. Common and uncommon urinary tract infections with relevant imaging findings and clinical relevance will be described and illustrated.

Background: Foreign body ingestion and food bolus impaction is a common clinical scenario and can present as an endoscopic emergency. Though majority of them pass spontaneously 10-20% require endoscopic intervention. Flexible endoscopy is recommended as therapeutic measure with minimal complications. The aim of our study is to present 5 years’ experience in dealing with foreign bodies in the upper gastrointestinal tract.Methods: Cases of foreign body ingestion admitted to department of general surgery from March 2015 to March 2020 were evaluated. The patients were reviewed with details on age, sex, type of FB, its location in gastrointestinal tract, treatment and outcome.Results: A total of 55 cases were studied. Age range was 1-85 years. Males were predominant 61.81%. Coins were found most commonly 63.6%. Esophagus was the commonest site of FB lodgement 70.9%. Upper esophagus being the most common 36.36%. Upper gastrointestinal flexible endoscopy was useful in retrieving FB in all the 55 cases. There were no complications throughout the study period.Conclusions: Flexible endoscopy should be used as definitive treatment and endoscopic treatment is safe and effective.

Chimeric Antigen Receptor-T (CAR-T) cell immunotherapy has produced dramatic responses in hematologic malignancies. One of the challenges in the field is the lack of a simple assay for the detection of CARs on the surface of immune effector cells. In this study, we describe a novel luciferase-based assay, termed Topanga Assay, for the detection of CAR expression. The assay utilizes a recombinant fusion protein, called Topanga reagent, generated by joining the extra-cellular domain of a CAR-target in frame with one of the marine luciferases or their engineered derivatives. The assay involves incubation of CAR expressing cells with the Topanga reagent, a few washes and measurement of luminescence. The assay can detect CARs comprising either immunoglobulin- or non-immunoglobulin-based antigen binding domains. We further demonstrate that addition of epitope tags to the Topanga reagent not only allows its convenient one step purification but also extends its use for detection of CAR cells using flow cytometry. However, crude supernatant containing the secreted Topanga reagent can be directly used in both luminescence and flow-cytometry based assays without prior protein purification. Our results demonstrate that the Topanga assay is a highly sensitive, specific, convenient, economical and versatile assay for the detection of CARs.

This investigation was aimed to study the influence of buck and PGF2α treatment on estrus synchronization in Surti does. Apparently healthy non-pregnant Surti does (n=18) were identified from the flock by Ultrasonography. They were evenly divided into 3 groups, 6 does in each group. The does of Treatment T1 group were teased with a sexually-active-apronized buck; the does of Treatment T2 group were treated with PGF2α, i.e., Inj. Lutalyse® @ 7.5 mg/doe IM twice, i.e. on day 0th and 11th, while the does of Control group T3 were kept without any treatment. The behavioural estrus was successfully synchronized by double injection of PGF2α at 11 days apart, as well as by buck effect in T2 and T1 groups, respectively. The induction of estrus was observed cent per cent in all the groups within one month. The mean time intervals between start of treatment and onset of estrus differed significantly between T1 (5.83±2.20 d) and T3 (14.67±2.76 d) groups. However, the mean duration of estrus was 29.83±0.91, 27.50±1.23 and 28.67±1.28 hrs and the mean number of services per conception was found 1.33±0.33, 1.50±0.50 and 1.33±0.33 for T1, T2 and T3 groups of Surti does, respectively, none differ significantly (p>0.05) between the groups. There was no significant difference in conception rates at first service amongst the groups (83.33%). The 17 does among 18 does (94.44 %) from all the three groups conceived within three services, irrespective of treatment groups. It was found that the buck effect appeared to be as effective as conventional PGF2α treatment in Surti does for synchronization of estrus

The serum progesterone and estradiol profiles during synchronization of estrus by buck effect and PGF2α treatments were monitored in Surti does. Total eighteen non-pregnant does selected were evenly divided into 3 groups, 6 does in each group. The does of Group I were teased with a sexuallyactive- apronized buck; and those of Group II were treated with PGF2α, i.e., Inj. Lutalyse® @ 7.5 mg/doe IM twice 11 days apart, while the Group III served as untreated control. Blood samples were collected from all the animals on day 0 (before 1st PGF2α injection), 3rd day (during treatment), 11th day (before 2nd PGF2α injection), 14th day (after treatment) and 40th day (post-service) by jugular vein puncture. The serum separated was stored at -20°C till further analysis. In all the three groups, 83.33% does, conceived at first service in the sampling cycle. The overall mean serum progesterone concentration of Group I does (5.82±0.72 ng/ml) was significantly higher (p less than 0.01) as compared to Group II (2.93±0.38 ng/ml) and III (2.88±0.30 ng/ml). Similarly, the overall mean serum progesterone concentration of Surti does on day 0 (2.65±0.46 ng/ml), 3rd (2.56±0.80 ng/ml), 11th (4.45±0.84 ng/ml) and 14th (3.40±0.63 ng/ml) did not differ significantly, but the overall mean level at day 40 (6.31±0.45 ng/ml) was significantly (p less than 0.01) higher, because most of animals became pregnant at that time. The overall mean serum oestradiol-17β levels of Group I (24.40±2.98 pg/ ml) was significantly higher (p less than 0.01) than in Group II (15.77±1.77 pg/ml) and III (12.21±1.45 pg/ ml). On the other hand, the overall mean serum oestradiol-17β levels of Surti does on day 0 (12.89±1.21 pg/ml), 3rd (15.84±1.74 pg/ml), 11th (14.81±1.96 pg/ml), 14th (22.15±2.97 pg/ml) and 40th (21.64±5.16 pg/ml) did not differ significantly (p>0.05) and the slightly higher overall mean level found at 40th day might be the influence of the non-pregnant does at first service in the cumulative animals. The hormonal profile reflected the initiation of cyclicity and establishment of pregnancy in treated and control animals.

Primary effusion lymphoma (PEL) is an aggressive type of non-Hodgkin lymphoma localized predominantly in body cavities. Kaposi's sarcoma-associated herpes virus (KSHV) is the causative agent of PEL. PEL is an incurable malignancy and has extremely poor prognosis when treated with conventional chemotherapy. Immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are Food and Drug Administration-approved drugs for the treatment of various ailments. IMiDs display pronounced antiproliferative effect against majority of PEL cell lines within their clinically achievable concentrations, by arresting cells at G0/G1 phase of cell cycle and without any induction of KSHV lytic cycle reactivation. Although microarray examination of PEL cells treated with lenalidomide revealed activation of interferon (IFN) signaling, blocking the IFN pathway did not block the anti-PEL activity of IMiDs. The anti-PEL effects of IMiDs involved cereblon-dependent suppression of IRF4 and rapid degradation of IKZF1, but not IKZF3. Small hairpin RNA-mediated knockdown of MYC enhanced the cytotoxicity of IMiDs. Bromodomain (BRD) and extra-terminal domain (BET) proteins are epigenetic readers, which perform a vital role in chromatin remodeling and transcriptional regulation. BRD4, a widely expressed transcriptional coactivator, belongs to the BET family of proteins, which has been shown to co-occupy the super enhancers associated with MYC. Specific BRD4 inhibitors were developed, which suppress MYC transcriptionally. Lenalidomide displayed synergistic cytotoxicity with several structurally distinct BRD4 inhibitors (JQ-1, IBET151 and PFI-1). Furthermore, combined administration of lenalidomide and BRD4 inhibitor JQ-1 significantly increased the survival of PEL bearing NOD-SCID mice in an orthotopic xenograft model as compared with either agent alone. These results provide compelling evidence for clinical testing of IMiDs alone and in combination with BRD4 inhibitors for PEL.

A simple, accurate, sensitive and robust assay that can rapidly and specifically measure the death of target cells would have applications in many areas of biomedicine and particularly for the development of novel cellular- and immune-therapeutics. In this study, we describe a novel cytotoxicity assay, termed the Matador assay, which takes advantage of the extreme brightness, stability and glow-like characteristics of recently discovered novel marine luciferases and their engineered derivatives. The assay involves expression of a luciferase of interest in target cells in a manner so that it is preferentially retained within the healthy cells but is either released from dead and dying cells or whose activity can be preferentially measured in dead and dying cells. We demonstrate that this assay is highly sensitive, specific, rapid, and can be performed in a single-step manner without the need for any expensive equipment. We further validate this assay by demonstrating its ability to detect cytotoxicity induced by several cellular and immune-therapeutic agents including antibodies, natural killer cells, chimeric antigen receptor expressing T cells and a bispecific T cell engager.

Introduction: Infective keratitis is an ocular emergency that requires prompt diagnosis for appropriate management. This study was done todetermine the sensitivity, specificity and predictive values of Gram stain and potassium hydroxide (KOH) wet mount in the diagnosis of suppurative keratitis. Materials and methods: A prospective hospital based study of all patients with clinically diagnosed suppurative keratitis presenting between January 2011 and June 2012 was carried out. Corneal scrapes were taken and subjected to direct microscopy and culture. Results: Corneal scrapings were obtained from 108 eyes with suppurative keratitis. Direct microscopy was positive in 39.2% of cases and organisms were grown in 50.9 % of the cases. Bacteria were responsible in 76.4% and fungi in 23.6%. Of the bacterial isolates, 66.7% was Staphylococcus aureus and of the fungal isolates, 30.7% was Aspergillus species. Sensitivity in vitro showed that Cefazolin, Chloramphenicol and Ofloxacin were most effective against bacteria. Sensitivity of Gram stain in detecting bacteria was 50% (95% CI, 34.43 to 65.56) and specificity was 77.3% (95% CI, 65.0 to86.3) and sensitivity of KOH wet mount in detecting fungi was 53.8% (95% CI, 26.12 to79.6) and specificity was 98.9% (95% CI, 93.44 to 99.9). Positivity of direct smear (65.1%) was found to be higher among eyes with larger ulcers (>2mm) than eyes with smaller ulcers (

Background and objectives: HIV/AIDS is a burning crisis worldwide. Cure of HIV is not yet possible so prevention is of prime importance in control of HIV. Education plays an important role in bringing awareness. This study is planned to find the existing knowledge and significance of educational intervention. Material and Methods : This study was an experimental design in which same group of subjects (students to class 9 and 10) of selected schools in Imadol, served as control and experimental group. Participants’ perception and knowledge about various aspects of HIV/AIDS were studied by noting their agreement with a set of 65 statements (questionnaire) using a modified Likert-type scale. The data was entered in SPSS. A p value less than 0.05 were taken as statistically significant. Result: In this study, educational intervention has proved statistically significant in public school (p value 0.02). Among different sub groups total median score for knowledge about HIV/AIDS and idea about vulnerable group was also statistically significant ( p value 0.01). Conclusion: Educational intervention does play significant role in strengthening knowledge and perception regarding issues related to HIV/AIDS. DOI: http://dx.doi.org/10.3126/jmcjms.v2i1.11418 Janaki Medical College Journal of Medical Sciences (2014) Vol. 2 (1):44-51

The DiseaseConnect (http://disease-connect.org )i s a web server for analysis and visualization of a comprehensive knowledge on mechanism-based disease connectivity. The traditional disease classification system groups diseases with similar clinical symptoms and phenotypic traits. Thus, diseases with entirely different pathologies could be grouped together, leading to a similar treatment design. Such problems could be avoided if diseases were classified based on their molecular mechanisms. Connecting diseases with similar pathological mechanisms could inspire novel strategies on the effective repositioning of existing drugs and therapies. Although there have been several studies attempting to generate disease connectivity networks, they have not yet utilized the enormous and rapidly growing public repositories of disease-related omics data and literature, two primary resources capable of providing insights into disease connections at an unprecedented level of detail. Our DiseaseConnect, the first public web server, integrates comprehensive omics and literature data, including a large amount of gene expression data, Genome-Wide Association Studies catalog, and text-mined knowledge, to discover disease–disease connectivity via common molecular mechanisms. Moreover, the clinical comorbidity data and a comprehensive compilation of known drug– disease relationships are additionally utilized for advancing the understanding of the disease landscape and for facilitating the mechanism-based development of new drug treatments.

Background Age-related macular degeneration (AMD) is a degenerative process that leads to severe vision loss. Wet AMD is defined by choroidal neovascularisation, leading to the accumulation of subretinal fluid (SRF), macular oedema (ME), and pigment epithelium detachments (PED). Purpose To evaluate the initial clinical experience of conversion from bevacizumab or ranibizumab to aflibercept in wet AMD patients. Methods Records of 250 consecutive wet AMD patients were retrospectively reviewed. Of 250 patients, 29 were naive (with no previous treatment), and 221 were previously treated with bevacizumab (1/3) or ranibizumab (2/3). On average, converted patients received 14 injections every 6 weeks on a treat-and-extend regimen with Avastin or Lucentis before being converted to aflibercept every 7 weeks on average (no loading dose) for three doses. For the purposes of this study, we concentrated on the patients converted to aflibercept since the number of naive patients was too small to draw any conclusion from. Snellen (as logMar) visual acuities, and optical coherence tomography (OCT) were compared predrug and postdrug conversion. Results Converted patients did not show a significant difference in visual acuity or average OCT thickness from preconversion values; however, small improvements in ME (p=0.0001), SRF (p=0.0001), and PED (p=0.008) grading were noted on average after conversion to aflibercept. Conclusions No significant difference in visual outcome or average OCT thickness was observed when switched from bevacizumab or ranibizumab q6 week to aflibercept 7-week dosing, on average. Mild anatomic improvements did occur in converted patients with regard to ME, SRF and PED improvement, on average, after conversion to aflibercept, and aflibercept was injected less frequently. No serious adverse reactions, including ocular infections or inflammation, as well as ocular and systemic effects were noted.

Pleomorphic adenoma (PA) can be defined as a benign mixed tumor composed of epithelial and myoepithelial cells arranged with wide cytomorphologic and architectural diversity and morphological patterns, demarcated from surrounding tissues by fibrous capsule. PA is one of the salivary gland tumors affecting both major and minor salivary glands. Parotid gland is the most commonly affected of the major group, and palate is the most common site of the minor salivary glands affected. The tumor has 3 components: an epithelial cell component; a myoepithelial cell component; and a mesenchymal component. The identification of these 3 components, which may vary quantitatively from one tumor to another, is essential to the recognition of pleomorphic adenoma. The tumor is also known as a benign mixed tumor. When these lesions affects the minor salivary glands on palate and if there is any involvement of the surrounding structures like maxillary antrum and nasal floor, then pre-operative imaging of these lesions is mandatory by 3-dimensional imaging modalities like CT or CBCT to evaluate the exact depth and the dimensions of the lesion. Following case of pleomorphic adenoma of palatal salivary glands which was evaluated with CT as well as CBCT pre- operatively.

Background Three de novo designed low molecular weight cationic peptides (IJ2, IJ3 and IJ4) containing an unnatural amino acid α,β-didehydrophenylalanine (∆Phe) exhibited potent antifungal activity against fluconazole (FLC) sensitive and resistant clinical isolates of Candida albicans as well as non-albicans and other yeast and filamentous pathogenic fungi. In the present study, their synthesis, susceptibility of different fungi and the mechanism of anti-candidal action have been elucidated. Methods The antimicrobial peptides (AMPs) were synthesized by solid-phase method and checked for antifungal activity against different yeasts and fungi by broth microdilution method. Anti-candidal mode of action of the peptides was investigated through detecting membrane permeabilization by confocal microscopy, Reactive Oxygen Species (ROS) generation by fluorometry, apoptosis and necrosis by flow cytometry and cell wall damage using Scanning and Transmission Electron Microscopy. Results and conclusions The MIC of the peptides against C. albicans and other yeast and filamentous fungal pathogens ranged between 3.91 and 250 μM. All three peptides exhibited effect on multiple targets in C. albicans including disruption of cell wall structures, compromised cell membrane permeability leading to their enhanced entry into the cells, accumulation of ROS and induction of apoptosis. The peptides also showed synergistic effect when used in combination with fluconazole (FLC) and caspofungin (CAS) against C. albicans. General significance The study suggests that the AMPs alone or in combination with conventional antifungals hold promise for the control of fungal pathogens, and need to be further explored for treatment of fungal infections.

Purpose: Kaposi sarcoma–associated herpes virus (KSHV)–associated primary effusion lymphomas (PEL) have extremely poor prognosis when treated with conventional chemotherapy. KSHV-encoded viral FLICE-inhibitory protein (vFLIP) K13 binds to the IkappaB kinase (IKK) complex to constitutively activate the NF-κB pathway, which has been shown to be essential for the survival and proliferation of PEL cells. The molecular chaperone HSP90 is a component of the IKK complex and is required for its activity. Experimental Design: We have analyzed the effect of HSP90 inhibitors on the survival and proliferation of PEL cells and on the activity of the NF-κB pathway. Results: We show that BIIB021, a purine scaffold–based orally administrable HSP90 inhibitor, shows preferential cytotoxicity toward PEL cells as compared with non-PEL cells. The cytotoxic effect of BIIB021 against PEL was associated with induction of cell-cycle arrest and apoptosis. BIIB021 blocked the expression of a number of cellular proteins involved in the regulation of cell cycle and apoptosis. BIIB021 also blocked constitutive NF-κB activity present in PEL cells, in part, by blocking the interaction of vFLIP K13 with the IKK complex subunits. In a xenograft model of PEL, BIIB021 significantly reduced tumor growth. Conclusion: BIIB021 blocks constitutive NF-κB activity in PEL and shows preferential antitumor activity against PEL in vitro and in vivo. BIIB021 may be a promising agent for treatment of PEL. Clin Cancer Res; 19(18); 5016–26. ©2013 AACR.

PURPOSE To evaluate the possible benefit of pars plana vitrectomy in the treatment of patients with endophthalmitis following antivascular endothelial growth factor (VEGF) injection. METHOD The authors retrospectively reviewed the medical records of all patients in their practice with a diagnosis of endophthalmitis from January 1, 2007, through December 31, 2011. Only those with a clinical presentation consistent with endophthalmitis after intravitreal anti-VEGF injection were included. Clinical data that were collected and recorded included visual acuities and the method of initial and subsequent treatment of endophthalmitis following anti-VEGF injection: tap and injection of intravitreal antibiotics (TAP) and tap and inject with subsequent pars plana vitrectomy (VIT). RESULTS The authors identified 23 patients meeting criteria. Nineteen patients had received bevacizumab and four patients had received ranibizumab. The median time from last injection to presentation was 4 days (range, 1-18 days) with a median follow-up of 15 months (range, 5-48 months) after being diagnosed of endophthalmitis. Nine patients had positive cultures. The median baseline visual acuity (preendophthalmitis) was 20/70 (range, 20/25 to counting fingers at 2 ft) with a median presenting visual acuity of counting fingers at 1 ft (range, 20/50 to light perception vision). Overall, 90% (9/10) of the patients in TAP only group regained visual acuity within 1 line or better of baseline versus 46% (6 of 13) in the TAP and VIT group. Only one of the patients treated with TAP alone suffered more than one line of visual acuity loss. CONCLUSION Patients diagnosed with endophthalmitis after anti-VEGF intravitreal injection who underwent TAP regained baseline visual acuity more often than those who underwent TAP and VIT. This study did not support a benefit for VIT in all patients, rather only in those cases who warranted it because of worsening clinical course. The study suggests that TAP is a viable primary intervention for endophthalmitis after anti-VEGF injection.