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Conventional tissue sampling can lead to misdiagnoses and repeated biopsies. Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1–2 mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1–2 mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging.

Introduction: Rational use of drugs against most common and life‑threatening tropical diseases such as malaria remains a huge challenge, particularly in sub-Saharan African region. The correct use of antimalarial drugs is the key not only to therapeutic success but also to deterring the spread of drug resistance malaria. Aims: To assess the physicians’ compliance with the national anti’-malaria treatment guidelines among Under five (U-5) years children in secondary health facilities in Sokoto metropolis. Methods: This was a cross-sectional study conducted as an exit interview among 292 mothers/caregivers of febrile U-5 children with antimalarial prescription, that presented to the out-patient clinics of the selected secondary health facilities in Sokoto metropolis. Simple random sampling technique using balloting option was used to select 2 secondary Health facilities in the metropolis, Proportionate allocation was done to allocate study subjects to the selected Health facilities based on average weekly outpatient attendance. The data was collected using an interviewer-administered questionnaire. Descriptive statistics was used to analysed data using IBM SPSS version 22. Results: Of the 292 children, only 115(39.4%) had malaria parasite test requested by the physician, out of which 63(54.8) had microscopy, while 52(45.2) of the children had malaria Rapid Diagnostic Test (mRDT). One hundred and eighty-five (65.1%) of the children were treated presumptively with anti-malarial drugs. Artemisinin based Combination Therapy (ACT) was prescribed in 221(77.8%) of the under-fives. The commonest prescribed ACT was Artemether-Lumefantrine in 113(77.4%) of the children. Majority 263(92.6%) of the prescriptions were in brand names. Recommendation: The physicians’ compliance with national malaria treatment guidelines using the proportion of U-5 children was suboptimal. There was over prescription of anti-malarial drugs, as majority of the patients treated for malaria had no laboratory evidence for the treatment. However, compliance with the use of ACT was good. This study shows also suboptimal compliance with WHO prescribing indicators with respect to prescription in generic names. Regular training of the health care providers by the government is recommended to improve adherence to antimalarial treatment guideline.

Background: Substance use is a global public health problem with increasing burden among university students. This study assessed the prevalence, pattern and risk factors of substance use among undergraduate students of Afe Babalola University, Ado-Ekiti, Nigeria.Methods: This was a cross-sectional study of undergraduate students of Afe Babalola University, Ado-Ekiti. A multi-stage sampling technique was used to select respondents. Data collection tool was a structured self-administered questionnaire. Data analysis was done using Statistical Package for the Social Sciences (SPSS) version 23. Statistical significance was set at p value

Sentinel lymph node biopsy (SLNB) is often omitted in selected patients with advanced primary melanoma, although the justification/criteria for omission have been debated. We sought to determine whether assessment of frailty could serve as an objective marker to guide selection for SLNB in patients with advanced primary melanoma. Patients presenting with clinical stage IIC (ulcerated, > 4 mm Breslow thickness) cutaneous melanoma from January 1999 through June 2019 were included. Frailty was assessed using the Memorial Sloan Kettering Frailty Index (MSK FI), a composite score of functional status and medical comorbidities. Five-year melanoma-specific survival (MSS) and overall survival (OS) were estimated using Cox regression, and predictors of OS were identified using competing risk models. MSS did not differ between patients who did (n = 451) or did not undergo SLNB (n = 179) [63.2% vs. 65.0%, p = 0.14]; however, omission of SLNB was associated with decreased 5-year OS (29% vs. 44%, p

Background: Diabetes places extra-burden on those affected with the condition particularly in resource constraint settings. Inaccessibility to affordable diagnostic procedures poses a major challenge to the assessment of cardiovascular status in patients with type-2 diabetes in resource limited settings. The study was aimed at evaluating some easily accessible biochemical markers and anthropometric indices implicated in cardiovascular disease amongst T2DM patients.Methods: One hundred and sixty (160) type-2 diabetic patients grouped into type-2 diabetes only as group 1, type-2 diabetic patients diagnosed with hypertension as group 2, and eighty (80) age and sex-matched controls as group 3, were enrolled in a cross-sectional pattern. Biochemical parameters were assayed using standard laboratory methods. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 20.0 with statistical significance considered at p≤0.05.Results: The values obtained for diabetic groups were: Glycated Hemoglobin (HbA1c) 9.07±1.99, 10.15±4.98, Total Homocysteine (tHcy) 14.85±52.10, 28.35±100.35, high sensitivity C-reactive protein (hs-CRP) 6.72±6.78,10.00±11.15, Waist Circumference, 92.58±1.55, 93.65±18.91, Hip Circumference, 96.87±9.01, 98.96±20.33, Systolic Blood Pressure, 113.50±12.94, 135.50±22.72, Diastolic Blood Pressure, 70.75±8.57, 75.38±12.62, Body Mass Index, 25.40±4.70, 26.93±6.50 (among patients) and HbA1c 5.81±0.86, tHcy 0.75±1.44, hs-CRP 5.30±6.19, Waist Circumference 83.15±10.69, Hip Circumference 93.50±22.05, Systolic Blood Pressure, 113.50±10.20, Diastolic Blood Pressure, 77.00±7.19, Body Mass Index, 24.84±4.93 (among controls).Conclusion: The assessment of some cardio metabolic markers and anthropometric indices may provide easy and accessible tools for prediction and assessment of cardiovascular disease in patients with T2DM especially in resource poor settings.Annals of Medical Laboratory Science (2021) 1(1), 36 - 48

Introduction: Prescription practices for malaria have been shown to influence the emergence of resistance to antimalarial drugs. Appropriate antimalarial drug use contributes to reductions in morbidity and mortality due to malaria with a consequent socioeconomic benefit, thus the success of a new malaria treatment policy would depend on the adherence of health care providers and patients to treatment recommendations. This study aimed to determine the prescribing pattern of anti-malaria in primary health care facilities in Sokoto State. Methods: A cross sectional study was carried-out in the Primary Health Care facilities in Sokoto State. Screening of prescription forms from the patients who presented at the outpatient clinic during the period of the study in the selected health facilities was done at the point of exit, and only those with antimalarial prescription were consecutively selected. An interviewer administered questionnaire was used to obtained brief history of the illness among 276 respondents who were enrolled in to the study. Record of Rapid Diagnostic Test (mRDT) for the diagnosis of the malaria was obtained from the patients and or their caregivers. Data were analyzed using IBM® SPSS version 20 statistical packages. Results: Majority 85 (30.8%) of the respondents were aged ≤ 1-10 years followed by 21-30 years 81 (29.3) Of the 276 antimalarial prescription forms obtained from the respondents, artemisinin- based combination therapy (ACT) was 166 (60.1%) and monotherapy was 110 (39.9%). The commonest artemisinin-based combination therapy prescribed for the respondents was Artemether-Lumefantrine 141 (84.9%) followed by Artesunate- Amodiaquine 16 (9.6%). The commonest oral mono-therapy prescribed was Sulphadoxine-pyrimethamine 28 (75.7%) while the most prescribed injectable monotherapy was artemether 59 (80.8%). Rapid Diagnostic Test for malaria (mRDT) was done for 274 (99.3%) respondents; those with mRDT positive were 238 (86.9%). The commonest presenting symptoms was fever 274 (99.3%) flowed by headache 225 (80.7%) and loss of appetite 215 (77.9%). Conclusion: The pattern of antimalarial prescription observed in this study was mainly artemisinin-based combination therapy. However, antimalarial monotherapy is still being prescribed. There is need for regular training of the health care workers on the appropriate treatment of malaria using the national guideline for treatment of malaria. Regular supply and availability of ACTs in all health facilities across the state will ensure full compliance with national guideline for malaria treatment using ACTs.

Surgical resection is the treatment for early cutaneous melanoma and is often curative. Some patients, however, will subsequently relapse. High-risk features in the primary tumor and regional lymph node metastasis highlight patient subsets that are at increased risk for recurrent disease. Immunotherapy in the form of checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab have been shown to improve recurrence-free survival for node-positive melanoma in the adjuvant setting and will be the focus of this review.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

INTRODUCTION: Checkpoint inhibitors have improved outcomes in metastatic melanoma, with 4-year overall survival (OS) of 46% for anti-PD-1 alone or 53% in combination with anti-CTLA-4. However, the median progression free survival is 6.9 and 11.5 months, respectively. Many who progress have gone on to alternative treatments, including surgery, yet the outcome of patients selected for surgery after checkpoint blockade remains unclear. METHODS: Patients who were treated with checkpoint blockade from 2003 to 2017, followed by metastasectomy, were identified from a prospectively maintained institutional melanoma database. Response to immunotherapy was assessed at the time of surgery. Patients were categorized as having responding, isolated progressing, or multiple progressing lesions. RESULTS: Of the 237 total patients identified, 208 (88%) had stage IV disease and 29 (12%) had unresectable stage III disease at the start of immunotherapy. Median OS following first resection was 21 months. Median follow-up among survivors was 23 months. Complete resection at the first operation (n=87, 37%), was associated with improved survival compared with patients with incomplete resection (n=150, 63%) (median OS not reached (NR) versus 10.8 months, respectively; 95% CI: 7.3,14.8; p

Background: While harmaline has been used as a pharmacological model of essential tremor (ET) in rodents and pigs, less is known about the effects of this pharmacological treatment in awake-behaving non-human primates. In this study, we investigated the time-course, amplitude, frequency, and consistency of harmaline tremor in primates. Methods: Three rhesus macaques were administered doses of harmaline ranging from 2–12 mg/kg (i.m.), and tremorous movements were quantified with accelerometers. One subject was also trained to perform a self-paced cued reaching task, with task engagement assessed under harmaline doses ranging from 2–8 mg/kg (i.m.). Results: Whole-body tremors manifested within 30 minutes of threshold-dose administration, and peak oscillatory frequency ranged between 10–14 Hz. However, large differences in tremor intensity and intermittency were observed across individual subjects under similar dosing levels. Additionally, engagement with the reaching task was dependent on harmaline dose, with performance mostly unaffected at 2 mg/kg and with little task-engagement at 8 mg/kg. Discussion: We provide a detailed assessment of factors that may underlie the heterogeneous responses to harmaline, and lay out important caveats towards the applicability of the behaving harmaline-tremoring non-human primate as a preclinical model for ET. Highlights The harmaline-primate is revisited for its potential as a preclinical model of tremor. Spontaneous tremor was heterogenous in amplitude across subjects despite similar harmaline doses, action tremors were not consistently observed, and performance on a behavioral task degraded with higher dosages.

Background For many years now, inguinal hernia repair in children has been done either by the open approach or laparoscopically with laparoscopy having the edge in terms of cosmesis and postoperative pain. However, recent studies have called for a return of the open approach as it had a comparable result to laparoscopy with lesser cost. This study aims to compare the outcomes of the two approaches at our institution. Methods This is a retrospective analysis of the prospectively collected data of all patients aged between 6 months and 13 years who underwent open or laparoscopic inguinal hernia repair in the period between January 2017 and July 2019 at our institution. Results 155 patients were included in the study. 100 (64.5%) underwent open inguinal repair while 55 (35.5%) were done laparoscopically. There was no significant difference in the postoperative complications between the open and laparoscopic groups (P = 0.66). The overall mean operative time for the laparoscopic group and the open group is (45.7 ± 15.2, 45.5 ± 15.4 min, P = 0.83) respectively. However, a subgroup analysis showed a statistical difference in the operative time in bilateral hernias favoring the laparoscopic approach, (44 ± 13.2, 63.2 ± 26.4 min respectively, P = 0.049). Laparoscopy was also associated with shorter times to full recovery compared to the open group (4.7 days, 7.5 days, P = 0.013). Surprisingly, there was no difference in the cosmetic outcome between the two groups which is contrary to the published literature. Conclusions Laparoscopic inguinal hernia repair in children is a feasible and reproducible procedure. It permits the evaluation of the contralateral groin without further incisions. In our study, laparoscopy was superior in terms of operative time in bilateral hernias and the time to recovery. Finally, an added benefit to laparoscopy is that it offers more training opportunities for fellows and residents to improve their laparoscopic skills., Highlights • Laparoscopic inguinal hernia repair in children is a feasible and reproducible procedure. • Laparoscopy was superior in terms of operative time in bilateral hernias and the time to recovery. • Laparoscopic hernia repair in children offers more training opportunities for fellows and residents to improve their laparoscopic skills.

Author(s): Guo, Y; Ahn, M-J; Chan, A; Wang, C-H; Kang, J-H; Kim, S-B; Bello, M; Arora, RS; Zhang, Q; He, X; Li, P; Dechaphunkul, A; Kumar, V; Kamble, K; Li, W; Kandil, A; Cohen, EEW; Geng, Y; Zografos, E; Tang, PZ | Abstract: BackgroundTreatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries.Patients and methodsIn this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation.ResultsA total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (l1% versus 5%) and leukopenia (0% versus 5%).ConclusionsConsistent with the phase III LUX-Head a Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC.Clinical trial registrationClinicalTrials.gov identifier: NCT01856478.

Background Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma. The limited disease-free survival after chemotherapy has resulted in a poor prognosis. The outcomes data for high-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) for PEL are limited owing to the rarity of the disease. Patients and Methods The present study included 9 patients with PEL from 2 major academic centers. Of these patients, 4 had received auto-HCT after high-dose therapy. Of the 9 patients, 8 (89%) had immunodeficiency (7 with human immunodeficiency virus seropositivity; 1, a solid organ transplant recipient) at the diagnosis. Human herpesvirus-8 by immunohistochemistry was positive in 8 patients. Anthracycline-based combination chemotherapy was used as first-line treatment in 7 patients; 4 underwent auto-HCT after attaining first complete remission. Results The median follow-up of the surviving patients was 25 months (95% confidence interval [CI], 8%-29%). The 2-year progression-free and overall survival for the 8 patients who had received treatment was 58% (95% CI, 22%-95%) and 73% (95% CI, 41%-100%), respectively. The 2-year progression-free and overall survival for the patients who had received auto-HCT was 50% (95% CI, 1%-99%) and 75% (95% CI, 33%-100%), respectively. Of the 4 auto-HCT recipients, all had been in first complete remission at the time of autografting. The cumulative incidence of relapse was 50% (95% CI, 19%-100%). No deaths were attributable to auto-HCT at 2 years after autografting. Conclusion Despite the small sample size, our data have shown that consolidative auto-HCT is safe and effective and should be considered for eligible patients with PEL after demonstration of an objective response to induction chemotherapy. However, the high relapse rate remains a concern and warrants the development of new strategies to mitigate post-transplantation relapse.

Objective: Pancreatic β-cell dysfunction is described to be present at the diagnosis of type 2 diabetes mellitus (T2DM) and progressively deteriorated with disease duration. However, its progression is variable and potentially influenced by several factors. The Magnesium (Mg) deficiency mediates insulin resistance but reports regarding its role in pancreatic β-cell dysfunction are scarce and conflicting. The aim of this study was to evaluate Mg deficiency effect on pancreatic β-cell function in T2DM patients at a specialist hospital in north eastern Nigeria. Materials and Methods: Study subjects were categorized in to two groups according to plasma Mg levels; 34 subjects with hypomagnesemia and 45 subjects with normal magnesium levels. Fasting blood samples were analyzed for Mg, glucose and insulin. Pancreatic β-cell function was estimated as HOMA-β. Results: Degree of pancreatic β-cell function, as measured by HOMA-β, was significantly lower among T2DM subjects with hypomagnesemia compared to the subjects with normal magnesium levels (38.1± 5.5 vs. 41.2± 6.2, Pvalue< 0.05). Lower plasma Mg was associated with decreased pancreatic β-cell function among the study subjects independent of age, BMI and duration of diabetes. Conclusion: We concluded that among subjects with T2DM in this study, Mg deficiency might be linked with worsening of pancreatic β-cell function.

Background and objective Experimental models suggest the use of different therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal condition. This study evaluated the effects of conventional drug treatment and anti-TNF therapy in patients with RA on microbiological and periodontal condition, establishing the association of markers of periodontal infection with indexes of rheumatic activity. Materials and methods One hundred seventy nine individuals with RA were evaluated (62 with anti-TNF-. and 115 with only DMARDs). The periodontal evaluation included plaque and gingival indexes, bleeding on probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival plaque samples for microbiological analysis. Rheumatologic evaluations included a clinical examination, rheumatoid factor (RF), antibodies against cyclic-citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). Results Anti-TNF-alpha therapy influenced periodontal microbiota with a higher frequency of T. denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher extension of CAL (p=0.005), and anti-TNF-alpha therapy with methotrexate was associated with a lower extension of CAL (p=0.05). The use of corticosteroids exerted a protective effect on the number of teeth (p=0.027). The type of DMARD affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs titers were associated with the presence of red complex periodontal pathogens (p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05), and ESR was associated with a greater PD (p=0.044) and presence of red complex (p=0.030). Conclusion Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.

Background Two RCTs found no survival benefit for completion lymphadenectomy after positive sentinel lymph node biopsy compared with observation with ultrasound in patients with melanoma. Recurrence patterns and regional control are not well described for patients undergoing observation alone. Methods All patients with a positive sentinel node biopsy who did not have immediate completion lymphadenectomy were identified from a single-institution database (1995–2018). First recurrences were classified as node only, local and in-transit (LCIT) only, LCIT and nodal, or systemic. Regional control and factors associated with recurrence survival were analysed. Results Median follow-up was 33 months. Of 370 patients, 158 (42·7 per cent) had a recurrence. The sites of first recurrence were node only (13·2 per cent), LCIT only (11·9 per cent), LCIT and nodal (3·5 per cent), and systemic (13·8 per cent). The 3-year postrecurrence melanoma-specific survival rate was 73 (95 per cent c.i. 54 to 86) per cent for patients with node-only first recurrence, and 51 (31 to 68) per cent for those with initial systemic recurrence. In multivariable analysis, ulceration in the primary lesion (hazard ratio (HR) 2·53, 95 per cent c.i. 1·27 to 5·04), disease-free interval 12 months or less (HR 2·38, 1·28 to 4·35), and systemic (HR 2·57, 1·16 to 5·65) or LCIT and nodal (HR 2·94, 1·11 to 7·79) first recurrence were associated significantly with decreased postrecurrence survival. Maintenance of regional control required therapeutic lymphadenectomy in 13·0 per cent of patients during follow-up. Conclusion Observation after a positive sentinel lymph node biopsy is associated with good regional control, permits assessment of the time to and pattern of recurrence, and spares lymphadenectomy-related morbidity in patients with melanoma.

Background and importance Despite the clinical benefits of therapy with control point inhibitors in several malignancies, this inhibition is closely linked to a series of immune related adverse events (irAEs). The early detection and management of these is of vital importance. Aim and objectives To identify and describe irAEs with programmed cell death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors in clinical practice. Material and methods A retrospective, descriptive, observational study was conducted in a 400 bed hospital in patients treated with immunotherapy (IT) from 1 January 2016 to 30 October 2018. Variables were age, gender, type of tumour, stage, IT, irAEs and grade, cycles until irAE appearance, irAE treatment and IT suspension. The electronic medical history was reviewed in OrionClinic and IT treatment in Farmis-Oncofarm. The causality of irAEs was ascertained on the basis of the European Society for Medical Oncology (ESMO) algorithms. Statistical analysis was performed with SPSS V.15. Results A total of 127 patients were treated with an average age of 65 years (range 36–88) and 75% were women: 76% of patients had non-microcytic lung cancer, 7% head–neck, 6% bladder, 5% breast, 4% renal, 2% melanoma and colorectal cancer. In 67% of patients, stage IV tumours were found, in 27% stage III, in 4% stage II and in 2% stage I. Nivolumab was prescribed in 54% of patients, pembrolizumab in 26%, atezolizumab in 13% and durvalumab in 7%. Fifty-two irAEs were identified. The average number of cycles until irAE appearance was 3.25 (range 1–57). The main irAEs were cutaneous (37%), gastrointestinal (23%), pneumonitis (14%) and endocrinological (8%); 64% grade I, 25% grade II, 12% grade III and no grade IV. Treatment was given for 66% of irAEs: oral corticoids (52%), topical corticoids (17%), antihistamines (12%) and hormone replacement therapy (5%). IT was resumed in 83% of patients. By the end of the study period, 31% of patients remained on therapy. Non-continuity was due to progression (55%), irAEs (10%) and other reasons (4%). Conclusion and relevance The most frequent irAEs in patients receiving IT were cutaneous and gastrointestinal, mostly transitory and grades I–II. They were mostly resolved with corticotherapy and antihistamines. Management of irAEs was presented on the basis of clinical experience; cooperation of patients, caregivers and healthcare professionals is required to watch over their safety to obtain the maximum efficacy with the lowest irAEs possible. References and/or acknowledgements No conflict of interest.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN Guidelines Panel meets at least annually to review comments from reviewers within the NCCN Member Institutions, examine relevant data, and reevaluate and update the recommendations. These NCCN Guidelines Insights summarize recent updates centered on treatment considerations for relapsed/refractory classic HL.

Introduction: Vyxeos® is a liposomal formulation employing a 1:5 molar ratio of daunorubicin:cytarabine. Clinical trials in high risk acute myeloid leukemias demonstrated a significant benefit in CR rates and median OS, culminating in FDA approval August 2017. Emerging pediatric data suggest this benefit may extend to acute lymphoblastic leukemia (ALL). The following pilot trial was performed to better understand the activity and toxicity profile in adults with relapsed and refractory ALL. Methods: Adults with ALL or mixed phenotype leukemia were eligible if >5% lymphoblasts and/or extramedullary disease >1x1cm. Induction consisted of Vyxeos 100 units/m2 on days 1, 3 and 5. Those with clinical benefit could receive up to 3 cycles of consolidation delivered at 65 units/m2 on days 1 & 3 after recovery of neutrophils (>500 cells/uL) and platelets (>50,000 cells/uL). Response: 11 patients (pts) have been treated to date, with median age of 39y (22-74y), 9 male, and 3 Caucasian. Six pts had B-ALL, including 1 B-myeloid. Four of 5 T-ALL pts had early T-cell precursor (ETP) phenotype. NGS was available in 9 pts, and included TP53 mutation (n=4), and PH-like changes (n=2). Median prior lines of therapy was 3, with 7 pts showing primary refractory disease. Prior blinatumomab, inotuzumab, CAR-T cell therapy, and allogeneic transplant were noted in 5, 2, 1, and 3 pts. Pancytopenia was uniform during induction, with febrile neutropenia noted in 9 pts. One pt passed from pneumonia after moving to comfort measures in lieu of intubation 20 days after Vyxeos, and is non-evaluable for response. A second pt developed grade 3 sepsis. The remainder of infections were grade 1-2. One pt had grade 3 gastrointestinal bleed, and 3 pts had grade 1 spontaneous subdural bleeding. One pt developed recurrent pericarditis in setting of anterior mediastinal mass. One case of veno-occlusive disease was observed in a pt with prior allogeneic transplant and inotuzumab. Median time to ANC recovery was 33.5 days among 10 evaluable pts. Two pts with refractory disease failed to recover platelets; among the remaining pts, median time to platelet recovery was 30.5 days. Adverse events were uncommon during consolidation, and include foot cellulitis and myopericarditis, each in 1 pt. Among 10 evaluable pts, 3 achieved CR/CRi, including 2 ETP T-ALL and one B-ALL. Two pts with TP53 mutation demonstrated >50% blast reduction with hematologic recovery, allowing for prolonged time to subsequent therapy. Four pts received 1-3 cycles consolidation. One pt was bridged to donor leukocyte infusion. Responses were noted in only 2 pts after progression following Vyxeos, highlighting refractory status of those enrolled. Median PFS was 57 days (95%CI: 10, 105), time to next therapy 76 days (95%CI: 47, 105), and OS 223 days (95%CI: 144, 302). Conclusions Vyxeos in high-risk refractory adult ALL was overall well tolerated and active, with median OS of approximately 7.5 months in this pilot trial. Confirmation of benefit in a larger study is warranted, incorporating a second induction course and/or the addition of novel agents to further improve on remission rate and duration of response. Disclosures Shah: Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Servier Genetics: Other; BeiGene: Consultancy, Honoraria; Acrotech/Spectrum: Honoraria; Pharmacyclics/Janssen: Honoraria, Other: Expenses; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Precision Biosciences: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Other: Expenses; Pfizer: Consultancy, Other: Expenses; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy. Chavez: Astra Zeneca: Research Funding; Novartis: Consultancy; Merck: Research Funding; Morphosys: Speakers Bureau; Adaptive Biotech: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Beigene: Speakers Bureau; Kite/Gilead: Consultancy; karyopharm: Consultancy; Epizyme: Speakers Bureau; Abbvie: Consultancy. Sokol: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Lancet: Celgene/BMS: Consultancy; Millenium Pharma/Takeda: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy; BerGenBio: Consultancy; ElevateBio Management: Consultancy; Agios: Consultancy; Astellas: Consultancy; Jazz: Consultancy. OffLabel Disclosure: Vyxeos is being evaluated in the described trial for the treatment of relapsed or refractory acute lymphoblastic leukemia in adults.

The COVID-19 pandemic has hugely impacted global public health and economy. The COVID-19 has also shown potential impacts on maternal perinatal and neonatal outcomes. This systematic review aimed to summarize the evidence from existing systematic reviews about the effects of SARS-CoV-2 infections on maternal perinatal and neonatal outcomes. We searched PubMed, MEDLINE, Embase, and Web of Science in accordance with PRISMA guidelines, from 1 December 2019 to 7 July 2021, for published review studies that included case reports, primary studies, clinical practice guidelines, overviews, case-control studies, and observational studies. Systematic reviews that reported the plausibility of mother-to-child transmission of COVID-19 (also known as vertical transmission), maternal perinatal and neonatal outcomes, and review studies that addressed the effect of SARS-CoV-2 infection during pregnancy were also included. We identified 947 citations, of which 69 studies were included for further analysis. Most (>70%) of the mother-to-child infection was likely due to environmental exposure, although a significant proportion (about 20%) was attributable to potential vertical transmission of SARS-CoV-2. Further results of the review indicated that the mode of delivery of pregnant women infected with SARS-CoV-2 could not increase or decrease the risk of infection for the newborns (outcomes), thereby emphasizing the significance of breastfeeding. The issue of maternal perinatal and neonatal outcomes with SARS-CoV-2 infection continues to worsen during the ongoing COVID-19 pandemic, increasing maternal and neonatal mortality, stillbirth, ruptured ectopic pregnancies, and maternal depression. Based on this study, we observed increasing rates of cesarean delivery from mothers with SARS-CoV-2 infection. We also found that SARS-CoV-2 could be potentially transmitted vertically during the gestation period. However, more data are needed to further investigate and follow-up, especially with reports of newborns infected with SARS-CoV-2, in order to examine a possible long-term adverse effect.

Context/Objective Marginal zone lymphoma (MZL) is an indolent non-Hodgkin lymphoma (NHL) accounting for 8–12% of NHL. Extra-nodal MZL (EMZL) is the most common subgroup, comprising ~70% of cases. Bendamustine and rituximab (BR) are commonly used as frontline therapy based on trials involving other indolent NHL, mainly follicular NHL. No trials have prospectively assessed frontline BR specifically in EMZL. We retrospectively report outcomes among EMZL patients receiving frontline BR. Design All patients with EMZL receiving frontline BR between 2011–2021 were identified in tumor registry. Treatment responses were assessed per 2007 Cheson criteria. Statistical analysis was performed using SPSS. Results Twenty-five patients met inclusion criteria. Median age was 69 years (40–81). Patients were White (80.0%), Asian (4.0%), or Other (16.0%). Five patients (20.0%) were stage I/II, and 19 (76.0%) were stage III/IV. MALT-IPI was low, intermediate, and high risk in 2 (10.5%), 9 (37.5%), and 8 (42.1%) patients, respectively. ECOG was Conclusion BR is safe/effective as frontline therapy for patients with EMZL. Responses were similar to previous reports of frontline BR in other indolent lymphomas.

This portion of the NCCN Guidelines for Hodgkin lymphoma (HL) focuses on the management of classical HL. Current management of classical HL involves initial treatment with chemotherapy or combined modality therapy followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale). The introduction of less toxic and more effective regimens has significantly advanced HL cure rates. However, long-term follow-up after completion of treatment is essential to determine potential long-term effects.

Background: The aim of this study was to evaluate the outcomes of priming salvage radioimmunotherapy (RIT) with a low dose of external beam radiotherapy (EBRT) in patients with relapsed low grade non-Hodgkin lymphoma (LG-NHL). Methods: Patients who received salvage RIT with or without 2 × 2 Gy EBRT between March 2009 and February 2013 were retrospectively reviewed at a single institution. Planning target volume (PTV) for EBRT was created by adding a 1–2 cm expansion to the gross tumor volume depending on the anatomical location. Kaplan−Meier method via log-rank was employed to analyze the endpoints freedom from progression (FFP) and overall survival (OS). Results: We identified 22 patients who received salvage RIT without chemotherapy with a median follow up of 34 months. Of these, 9 (41%) patients were treated with EBRT immediately prior to RIT, and 13 (59%) received salvage RIT alone. Median FFP was not reached in patients who underwent combination treatment, while it was 9 months for patients treated with RIT alone ( p = 0.02). OS for all patients at 36 months was 80.3% with no significant difference between the two groups ( p = 0.88). On univariate analysis, the addition of EBRT was associated with improved FFP [hazard ratio (HR) = 4.17; 95% confidence interval (CI), 1.24–19.1; p = 0.02)]. No long term toxicities were reported in both groups. Conclusions: RIT outcomes and effects were improved with addition of low-dose EBRT immediately prior to it, in the treatment of relapsed LG-NHL with no additional toxicity. This study is hypothesis-generating and the findings should be validated in prospective studies.

Introduction Ibrutinib was FDA approved for relapsed or refractory (R/R) marginal zone lymphoma (MZL) based on a phase II clinical trial that showed an overall response rate of 48% (Noy et al, Blood 2017). However, factors associated with response to ibrutinib in R/R MZL and outcomes of patients after progression on ibrutinib are unknown. Given the poor survival in other B-cell lymphomas such as mantle cell lymphoma (MCL) after progression on ibrutinib (Martin P et al, Blood 2016), we sought to evaluate clinicopathologic characteristics predictive of ibrutinib failure in R/R MZL, and describe outcomes of patients who experienced progression on ibrutinib therapy. Methods We performed a multicenter retrospective study of MZL patients treated at 19 US medical centers. Eligible patients were ≥ 18 years diagnosed with MZL from 2010-2019, who received ibrutinib for R/R MZL. Patients achieving a complete response (CR) or partial response (PR) with ibrutinib were considered ibrutinib responders, while those who had stable disease (SD) or progression of disease (PD) were classified as non-responders. The primary endpoint was to evaluate factors predictive of primary progression (PD) on ibrutinib. Secondary endpoints include evaluation of predictors of overall survival (OS) and progression-free survival (PFS) following ibrutinib therapy, assessment of outcomes based on the sequencing of ibrutinib therapy, and evaluation of outcomes following ibrutinib failure. PFS was defined as time from the start of ibrutinib therapy until lymphoma relapse/progression or death from any cause, censoring at last clinical assessment if no progression or death. OS was defined as time from the start of ibrutinib treatment until death or last follow-up. A multivariable Poisson regression analysis was performed to model ibrutinib progression on the clinicopathologic factors (see Table). To identify significant predictors for OS and PFS, we used a multivariable Cox model. Results 101 patients with R/R MZL received ibrutinib, of whom 99 had sufficient data for inclusion in the analysis. Among these patients, 63% (n=62) had CR/PR to ibrutinib (ibrutinib responders, CR=17, PR=45) and 37% (n=37) had no response (ibrutinib non-responders, SD=25, PD=12). The median duration of follow-up was 1.8 years (range=0.1-5.4 years) and 2 years (range=0.2-6.3 years) for ibrutinib responders and non-responders, respectively. Baseline characteristics of the R/R MZL patients stratified by ibrutinib response are shown in the Table. Among all the baseline factors examined for association with ibrutinib progression, only primary refractory disease (refractory to frontline therapy, RR=3.78, 95%CI=1.36-10.45, p=0.01) was predictive of a higher probability of primary progression on ibrutinib on multivariable analysis. The median OS was significantly better for responders (NR [not reached], 95%CI=3.2-NR) compared to non-responders (3.4 years, 95%CI=1.4-NR) (Figure 1A). Achieving CR/PR with ibrutinib (HR=0.22, 95%CI=0.09-0.52) and lack of complex cytogenetics (HR=0.22, 95%CI=0.08-0.59) were predictors of superior PFS. Similarly, ibrutinib response (HR=0.13, 95%CI=0.03-0.53) and lack of complex cytogenetics (HR=0.19, 95%CI=0.04-0.87) were predictors of better OS. There was no difference in PFS or OS based on the timing of ibrutinib administration (second vs third vs fourth line and beyond, Figure 1B and 1C). The median post ibrutinib relapse/progression OS (PROS) for patients who initially responded then progressed on ibrutinib (secondary progression, n=19) was 4 years (Figure 1D). The median PROS for patients who had no response to ibrutinib were stratified according to SD vs PD. The median PROS for those who had SD was NR and those with PD was 0.1 year (Figure 1E). Conclusion This is the largest series of R/R MZL patients treated with ibrutinib. A history of primary refractory disease was predictive of primary progression on ibrutinib, while the presence of complex cytogenetics was associated with inferior PFS and OS. In contrast to MCL, the outcomes of patients who progress on ibrutinib in R/R MZL are not poor except for the primary progression cohort (those with PD as the best response to ibrutinib). Improving therapeutic options for patients who experience PD with ibrutinib treatment represents an urgent unmet need and these patients should be prioritized for evaluation of novel therapeutic approaches. Figure Disclosures Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Reddy:Genentech, BMS: Research Funding; KITE Pharma, Abbvie, BMS, Celgene: Consultancy. Caimi:Genentech: Research Funding; Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding. Greenwell:Lymphoma Research Foundation: Research Funding; Acrotech Biopharma LLC, Kyowa Kirin: Consultancy. Janakiram:Takeda, Fate, Nektar: Research Funding. Olszewski:Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Palmisiano:AbbVie: Research Funding; Genentech: Research Funding. Awan:Genentech: Consultancy; Janssen: Consultancy; Astrazeneca: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Gilead Sciences: Consultancy; Kite Pharma: Consultancy; Dava Oncology: Consultancy; Celgene: Consultancy; Blueprint medicines: Consultancy; Sunesis: Consultancy; Karyopharm: Consultancy; MEI Pharma: Consultancy. Barta:Monsanto: Consultancy; Atara: Honoraria; Seattle Genetics: Honoraria, Research Funding; Janssen: Honoraria; Pfizer: Honoraria. Grover:Genentech: Research Funding; Tessa: Consultancy. Bartlett:Roche/Genentech: Consultancy, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed Therapeutics: Research Funding; Acerta: Consultancy; BTG: Consultancy; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding; Merck: Research Funding; Forty Seven: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; ADC Therapeutics: Consultancy; Autolus: Research Funding; BMS/Celgene: Research Funding. Christian:Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Herrera:Pharmacyclics: Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Karyopharm: Consultancy.

Management of regional lymph nodes in patients with melanoma has evolved significantly in recent years. The value of nodal intervention, long utilized for its perceived therapeutic benefit, has now shifted to that of a critical prognostic procedure used to guide clinical decision making. This review focuses on the three landmark, randomized controlled trials evaluating the role of surgery for regional lymph nodes in melanoma: Multicenter Selective Lymphadenectomy Trial I (MSLT-I), German Dermatologic Cooperative Oncology Group-Selective Lymphadenectomy Trial (DeCOG-SLT), and Multicenter Selective Lymphadenectomy Trial II (MSLT-II).

Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiation is standard therapy for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin-induced lung injury and radiation toxicity. Brentuximab vedotin is highly active in relapsed HL and was recently approved with doxorubicin, vinblastine, and dacarbazine (AVD) for previously untreated stage III/IV HL. We evaluated brentuximab-AVD for nonbulky stage I/II HL in a multicenter phase 2 study. Patients received a lead-in cycle of brentuximab vedotin monotherapy on days 1 and 15, followed by an exploratory positron emission tomography/computed tomography scan. Patients then received brentuximab-AVD for 4 to 6 cycles based on interim positron emission tomography/computed tomography scanning after cycle 2. Thirty-four patients were enrolled with a median age of 36 years (range, 20-75 years). Risk was early favorable in 62% and unfavorable in 38%. The best complete response rate was 100%. At a median follow-up of 38 months, the progression-free survival and overall survival were 94% and 97%, respectively. The most common adverse events were peripheral sensory neuropathy (79%), neutropenia (76%), fatigue (74%), and nausea (71%). The most common grade 3/4 toxicities were neutropenia (62%), febrile neutropenia (35%), and peripheral sensory neuropathy (24%). One elderly patient died of neutropenic sepsis in the first brentuximab-AVD cycle. Brentuximab dose reductions were required in 38% of patients, most for peripheral neuropathy. In conclusion, brentuximab-AVD without bleomycin or radiation produced a high complete response rate, with most patients requiring only 4 total cycles of therapy. Because toxicity was higher than would be expected from AVD alone, this method may not be appropriate for early-stage patients with a highly favorable prognosis. This trial was registered at www.clinicaltrials.gov as #NCT01534078.

Autism Spectrum Disorder (ASD), often referred to as Autism, is a clinically heterogeneous neurodevelopmental disorder with core-defining features of impaired socialization, impaired verbal and nonverbal communication, and restricted and repetitive patterns of behaviour. The disorder is presently diagnosed behaviourally, however the search for possible biomarkers that could aid earlier diagnosis have been on the increase. The present study aims to investigate plasma amino acid levels as a potential biomarker in ASD screening. Plasma levels of 20 amino acids (AA) (including neurotransmitters-GABA and glutamate) of autistic individuals and typical age and sex matched control, were determined using reversed-phase high performance liquid chromatography (RPHPLC). All statistical analyses (independent t-test, spearman correlation, cohen’s d effect size) were done using IBM SPSS version 20. A total of 31 plasma samples (18 Autism cases and 13 agesex matched controls) were analyzed with mean ages 8.44±4.87 for cases and 8.15±4.88 for controls. No significant intergroup difference was observed in the individual amino acid levels with the exception of glutamate (t = 5.472, df = 2.324, p = 0.000063), glutamine (t = 8.342, df = 14.780, p = 0.000001) , GABA (t = 6.601, df = 24.593, p = 0.000001), tryptophan (t = 3.568, df = 16.472, p = 0.002) and cysteine (t = 4.000, df = 13.762, p = 0.001).The amino acid profile and the glutamate - GABA levels can serve as biochemical markers for ASD, and can thus be utilized as screening for earlier diagnosis of the disorder. Keywords: Autism Spectrum Disorder (ASD), Biomarkers, Neurotransmitters, GABA, Glutamate, Diagnosis

Sentinel lymph node biopsy (SLNB) is recommended for patients with intermediate-thickness melanoma, but the use of SLNB for patients with thick melanoma is debated. This report presents a single-institution study investigating factors predictive of sentinel lymph node (SLN) metastasis and outcome for thick-melanoma patients .A retrospective review of a single-institution database from 1997 to 2012 identified 147 patients with thick primary cutaneous melanoma (≥4 mm) who had an SLNB. Clinicopathologic characteristics were correlated with nodal status and outcome.The median age of the patients was 67 years, and 61.9 % of the patients were men. The median tumor thickness was 5.5 mm, and 54 patients (36.7 %) had a positive SLN. Multivariable analysis showed that only tumor thickness significantly predicted SLN metastasis (odds ratio 1.14; 95 % confidence interval (CI) 1.02-1.28; P = 0.02). The overall median follow-up period was 34.6 months. Overall survival (OS) and melanoma-specific survival (MSS) were significantly worse for the positive versus negative-SLN patients. Multivariable analysis showed that age [hazard ratio (HR) 1.04; 95 % CI 1.01-1.07; P = 0.02] and SLN status (HR 2.24; 95 % CI 1.03-4.88; P = 0.04) significantly predicted OS, whereas only SLN status (HR 3.85; 95 % CI 2.13-6.97; P 0.01) significantly predicted MSS.Tumor thickness predicts SLN status in thick melanomas. Furthermore, SLN status is prognostic for OS and MSS in thick-melanoma patients, with positive-SLN patients having significantly worse OS and MSS. These findings show that SLNB should be recommended for thick-melanoma patients, particularly because detection of SLN metastasis can identify patients for potential systemic therapy and treatment of nodal disease at a microscopic stage.

Background Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder with frequent extranodal presentation and involvement of the respiratory system. The purpose of this study is to describe the clinical characteristics, pathologic findings, and treatment outcomes of LYG in a single tertiary institution. Methods This is a retrospective review of series of cases of LYG diagnosed at Moffitt Cancer Center (MCC) between 2000 and 2011. We describe clinical presentation, histopathologic findings, and treatment outcomes. Results We identified 11 cases of biopsy-proven LYG at our institution. All patients presented with lung involvement by LYG. Nine patients were treated with rituximab-based chemotherapy. The overall response rate was 63.6% (complete response rate, 36.44%). Extra-pulmonary involvement was common (central nervous system, kidney, adrenal glands, testicles, and liver). The median overall survival and progression-free survival were 23 and 12.2 months, respectively. Conclusions LYG is a rare B-cell lymphoproliferative disorder with involvement if the respiratory system. The presentation is heterogeneous, and response to therapy is variable. Although it is considered a poor prognosis disease, long-term survivors in remission have been described.

The objective of this study was to determine the effects of AA and energy intake during late gestation on piglet birth weight and reproductive performance of high-performing (14.5 total born) gilts and sows housed under commercial conditions. At d 90 of gestation, a total of 1,102 females (PIC 1050) were housed in pens by parity group (gilts or sows) with approximately 63 gilts and 80 sows in each pen, blocked by BW within each pen, and each female was randomly assigned to dietary treatments within BW block. Dietary treatments consisted of combinations of 2 standardized ileal digestible (SID) AA intakes (10.7 or 20.0 g/d SID Lys and other AA met or exceeded the NRC [2012] recommendations) and 2 energy intakes (4.50 or 6.75 Mcal/d intake of NE) in a 2 × 2 factorial arrangement. Data were analyzed using generalized linear mixed models specified to recognize pen as the experimental unit for parity and the individual female as the experimental unit for dietary treatments. Results indicate an overall positive effect of high energy intake on BW gain during late gestation, although this effect was more manifest under conditions of high, as opposed to low, AA intake (interaction, < 0.001). Furthermore, the magnitude of BW gain response to increased energy intake was greater ( < 0.001) for sows compared with gilts. Sows fed high energy intake had a reduced probability of piglets born alive ( < 0.004) compared with those fed low energy, but no evidence for differences was found in gilts. This can be explained by an increased probability ( = 0.002) of stillborns in sows fed high energy intake vs. sows fed low energy intake. There were no evidences for differences among dietary treatments in litter birth weight and individual piglet birth weight of total piglets born. However, individual born alive birth weight was approximately 30 ± 8.2 g heavier ( = 0.011) for females fed high, as opposed to low, energy intake. Furthermore, piglets born alive were approximately 97 ± 9.5 g heavier ( < 0.001) for sows than for gilts. Preweaning mortality was decreased ( = 0.034) for females fed high AA intake compared with females fed low AA intake regardless of energy level. In conclusion, 1) BW gain of gilts and sows depended not only on energy but also on AA intake, 2) sows fed increased amount of energy had an increased stillborn rate, and 3) increased energy intake during late gestation had a positive effect on individual piglet birth weight with no evidence for such an effect for AA intake.

Diaphragmatic hernia following blunt abdominal injury is extremely rare and often diagnosed late. Missed diagnosis is also common with this condition. We herein present a delayed presentation of diaphragmatic hernia following blunt abdominal injury that was initially misdiagnosed as recurrent acute asthmatic attack due to repeated presentation with episodic difficulty in breathing.

Background: Randomized trials in the pre-rituximab era showed that watch and wait (WW) when compared to initial treatment (IT) for asymptomatic advanced-stage follicular lymphoma (FL) did not impact overall survival (OS). In the rituximab era, a randomized trial showed patients with advanced-stage, asymptomatic, low-burden FL were less likely to need chemotherapy at 3 years when treated with rituximab only at diagnosis compared to WW, however with no difference in OS (Ardeshna et al., 2014). In another analysis, there was no impact of WW compared to IT on the time to next anti-lymphoma therapy (Solal-Celigny et al., 2012). However, the existing studies were limited by sample sizes and not powered by survival. In addition, few patients with grade 3a FL were included, thus it is not clear if pathological grades (other than grade 3b) should be taken into consideration when choosing WW vs IT. Here we studied the outcomes of WW vs IT for patients with advanced-stage (stage III/IV) FL using the National Cancer Database (NCDB) and compared the outcomes by FL pathological grades. Methods: Patients diagnosed between 2011-2016 were included. We only included patients diagnosed after 2011 (when rituximab was FDA approved for FL as maintenance) so our results reflect the current management of FL. To ensure accurate reporting of IT, only patients who were diagnosed and initially managed at the reporting facility were included. Demographic characteristics were compared using Chi-square test for categorical variables and ANOVA for continuous variables. Univariate comparison of OS was conducted using Logrank test. Multivariate survival analysis was conducted using Cox proportional hazard model with the following covariates: age, gender, race, Hispanic ethnicity, stage, grade, existence of previous malignancies, comorbidity score, facility type, facility lymphoma patient volume, urban/rural location, education, income and insurance status. Results: A total of 14417 patients with stage III/IV FL were included. Among them, 10755 received IT (74.6%) and 3662 (25.4%) were managed by WW at diagnosis. For those who received IT, the median time to treatment was 35 days (IQR 22-56 days). Preliminary analyses showed that patients with grade 1 FL and grade 2 FL were managed similarly and had similar OS, therefore we combined grade 1 and grade 2 into grade 1-2 FL as opposed to grade 3 FL. A total of 13050 patients had grade 1-2 FL and 4286 patients had grade 3 FL. Patients with grade 1-2 FL were more likely to be managed by WW than those with grade 3 FL (29.8% vs 12.5%, respectively; p Patients on WW were older, more likely to be female, more likely to have previous malignancies, had higher education and income, and more likely to have private insurance or Medicare than Medicaid or no insurance (Table 1). Patients with grade 1-2 FL had similar OS when managed by WW compared to IT (5-year OS rate: 76.3% vs 76.2%, respectively; p=0.32; Figure 1). In contrast, patients with grade 3 FL had worse OS when managed by WW compared to IT (5-year OS rate: 65.3% vs 73.5%; p Other factors associated with OS are listed in Table 2. Conclusion: Our study confirms the findings of lack of OS benefits in patients with advanced stage, grade 1-2 FL when treated with WW versus IT. In contrast, patients with advanced stage, grade 3 FL had worse OS with WW approach. While the NCDB does not separate grade 3 FL into 3a and 3b, it is assumed that FL 3b is universally managed as DLBCL and receive IT given its more aggressive course. Under this assumption, all grade 3 FL patients on WW were likely grade 3a. Thus, our results suggest that grade 3a FL patients on WW had worse OS compared to grade 3 FL patients who received IT (see Figure 2 and its footnote for illustration). Although a definitive conclusion cannot be made regarding grade 3a FL, further studies to compare the outcome of WW vs IT with special focus on stage 3a FL are warranted. Disclosures Shah: NCCN: Vice-Chair, Acute Lymphoblastic Leukemia Working Group: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Precision Biosciences, Novartis, AstraZeneca: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Kite/Gilead, Celgene/Juno/BMS, Novartis, Pfizer, Amgen, Spectrum/Acrotech, Precision Biosciences, Beigene, AstraZeneca, Pharmacyclics/Jansen, Adaptive: Honoraria; Moffitt Cancer Center: Current Employment; Kite/Gilead, Jazz, Incyte: Research Funding. Bello:Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Sokol:EUSA Pharma: Consultancy, Honoraria, Speakers Bureau; Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kyowa/Kirin Inc.: Membership on an entity's Board of Directors or advisory committees. Pinilla Ibarz:Pharmacyclics: Consultancy, Speakers Bureau; Novartis: Consultancy; Sanofi: Consultancy; TG Therapeutics: Consultancy; Janssen: Consultancy, Speakers Bureau; Sunesis Pharmaceuticals: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Chavez:Karyopharm: Consultancy; BeiGene: Speakers Bureau; Bayer: Consultancy; Merck: Research Funding; Morphosys: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy; AbbVie: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Verastem: Consultancy; Pfizer: Consultancy.

Introduction: The management of classical Hodgkin lymphoma (cHL) with first line therapy continues to evolve resulting in some of the best outcomes in oncology. Around 20-30% of patients with cHL relapse and have to undergo salvage chemotherapy followed by autologous hematopoietic cell transplant (Auto HCT). There are no randomized trials comparing the most common regimens used in second line to date. With the introduction of newer agents in the treatment of cHL, it is essential to identify patients that might benefit from a different approach in first salvage setting. The aim of this study is to assess patterns of relapse and differences in outcomes based on salvage regimens. Methods: We retrospectively identified 193 consecutive patients with cHL treated in our academic medical center. Adult patients treated with ABVD (Adriamycin, Bleomycin, Vinblastine, Decarbazine) for first line were included. The three most common salvage regimens used in our institution included ICE (Ifosfamide, Carboplatin, Etoposide), ESHAP (Etoposide, Steroids, Ara-C, Cisplatin), or IGEV (ifosfamide, Gemcitabine, Vinorelbine). Patients were divided into two groups: those progressing during ABVD or relapsing within 1 year are considered (refractory) versus all other as (late-relapse). Response to salvage therapy and performance of Auto HCT were compared using Chi-square test. Univariate comparison of OS was conducted using Log-rank test. Results: The majority of patients were refractory to front line therapy (69%). As expected, there was predominance of male gender (61%), with median age of 35 yrs (range 13-68 yrs). The distribution of baseline characteristics did not seem to be different between the two groups (Table 1). Refractory patients were more likely to have B symptoms and higher ESR on presentation (Table 1). Of the refractory patients, the majority had initial response to therapy then relapsed within 1 year (65%). On Univariate analysis, late-relapse patients had better overall survival compared to refractory disease (13.5 yrs vs 9 yrs respectively) (p The majority of the patients in both groups received ICE as the primary regimen, followed by ESHAP and IGEV (Table 1). The CR rate was not statistically different among the three salvage regimens (ICE, ESHAP, IGEV as 37%, 29%, 53% respectively) (P=0.248). Late-relapses were more likely to obtain a complete response (CR) to salvage therapy (48% vs 32% respectively) (P=0.025). However, when CR rate stratified by salvage regimen, only refractory patients treated with ICE demonstrated statistically significant worse CR rate compared to late-relapse treated with ICE (32% vs 48% respectively) (P=0.047). The difference was not statistically different for ESHAP and IGEV. While there was a difference in CR rate between relapsed and refractory patients, the difference was not observed in the rate of consolidative Auto HCT between the two groups. On univariate analysis, Auto HCT was associated with improved median overall survival compared to no Auto HCT (11.3 yrs vs 1.6 yrs, respectively) (P Conclusions: To our knowledge, this is the largest retrospective comparison study on the outcome of the most common salvage chemotherapy regimens in cHL. Our study highlights the unmet need early introduction for novel non chemotherapy-based interventions in refractory patients. It also shows the consistent CR rate in real world experience in comparison with clinical trials and persistent need for Auto HCT in the salvage setting in the current chemotherapy era. Disclosures Chavez: BeiGene:Speakers Bureau;Bayer:Consultancy;Merck:Research Funding;Morphosys:Consultancy, Speakers Bureau;AstraZeneca:Speakers Bureau;Celgene:Consultancy;Novartis:Consultancy;AbbVie:Consultancy;Genentech:Speakers Bureau;Epizyme:Speakers Bureau;Gilead:Consultancy;Karyopharm:Consultancy;Kite, a Gilead Company:Consultancy, Speakers Bureau;Verastem:Consultancy;Pfizer:Consultancy.Shah:Kite/Gilead, Jazz, Incyte:Research Funding;Moffitt Cancer Center:Current Employment;NCCN: Vice-Chair, Acute Lymphoblastic Leukemia Working Group:Membership on an entity's Board of Directors or advisory committees;Kite/Gilead, Celgene/Juno/BMS, Novartis, Pfizer, Amgen, Spectrum/Acrotech, Precision Biosciences, Beigene, AstraZeneca, Pharmacyclics/Jansen, Adaptive:Honoraria;Kite/Gilead, Precision Biosciences, Novartis, AstraZeneca:Other: TRAVEL, ACCOMMODATIONS, EXPENSES.Sokol:EUSA Pharma:Consultancy, Honoraria, Speakers Bureau;Kyowa/Kirin Inc.:Membership on an entity's Board of Directors or advisory committees;Kymera Therapeutics:Membership on an entity's Board of Directors or advisory committees.Pinilla Ibarz:Takeda:Consultancy, Speakers Bureau;AstraZeneca:Consultancy, Speakers Bureau;Abbvie:Consultancy, Speakers Bureau;Novartis:Consultancy;Sunesis Pharmaceuticals:Consultancy;TG Therapeutics:Consultancy;Sanofi:Consultancy;Pharmacyclics:Consultancy, Speakers Bureau;Janssen:Consultancy, Speakers Bureau.Bello:Celgene:Consultancy, Honoraria, Speakers Bureau;Seattle Genetics:Consultancy, Honoraria, Speakers Bureau.

Tumor biology and careful patient selection weigh heavily in determining the appropriate role of surgical resection in stage IV melanoma. Historically, surgical resection for highly selected patients with metastatic melanoma was the only treatment modality associated with improved long-term survival and the ability to provide palliation. With the new age of effective systemic therapies, the treatment of metastatic melanoma has become more intricate and future work is needed to better define the role for surgery within the current treatment paradigm.

The 21-gene Oncotype DX® Breast Recurrence Score® (RS) assay has been prospectively validated as prognostic and predictive in node-negative, estrogen receptor-positive (ER+)/HER2− breast cancer patients. Less is known about its prognostic role in node-positive breast cancer. We compared RS results among patients with lymph node-negative (N0), micrometastatic (N1mi), and macrometastatic (N+) breast cancer to determine if nodal metastases are associated with more aggressive biology, as determined by RS. Overall, 610,350 tumor specimens examined by the Genomic Health laboratory from February 2004 to August 2017 were studied. Histology was classified centrally, while lymph node status was determined locally. RS distribution (low

Antibiotics are used by the veterinarians and poultry industry to enhance growth rates, health of the birds, feed efficiency, egg production and for therapeutic reasons to reduce the incidence of poultry diseases. Antibiotics had been used in poultry production for both therapeutic and prophylactic purposes. Most poultry farmers in Nigeria have employed the use of various antibiotics with or without the guidance of veterinarians. Although antibiotics benefit most of its uses, the illegal use of these drugs has led to the accumulation of toxic antibiotic residues in edible poultry products destined for human consumption. And this poses a major threat and hazard to the public that could be toxicological, microbiological or immunological. Several analytical techniques are available to screen edible poultry products with levels of toxic antibiotic residues. Drug withdrawal period and maximum residue level of antibiotics should be strictly observed in treated birds before any poultry product (meat or eggs) is passed ＂wholesome＂ for human consumption. There are still few researches addressing this major public health problem coupled with lack of awareness in Nigeria. Therefore, there is need for public enlightenment campaign on the dangers of antibiotic residues in edible poultry tissues and products to the teeming populace and restriction and regulation of indiscriminate use of antibiotics in poultry production and industry to curb the incidence of this public health hazard in Nigeria.

Hodgkin lymphoma (HL) is an uncommon malignancy involving lymph nodes and the lymphatic system. Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma are the 2 main types of HL. CHL accounts for most HL diagnosed in the Western countries. Chemotherapy or combined modality therapy, followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale), is the standard initial treatment for patients with newly diagnosed CHL. Brentuximab vedotin, a CD30-directed antibody-drug conjugate, has produced encouraging results in the treatment of relapsed or refractory disease. The potential long-term effects of treatment remain an important consideration, and long-term follow-up is essential after completion of treatment.

Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30(+) NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.gov as #NCT01421667.

The adjustable sitting inclination rehabilitation chair was fabricated with mild steel and soft upholstered fabric was used for the overlay on the seat, headrest and armrest. The components were coupled with a linear actuator at the upper frame for the reclining of the backrest about it axis. The wheels are located outboard of the seat of the chair to enhance stability while foot rest supports the posterior weight of the users. The narrow seat allows free movement of the leg when the user is seated. Sitting inclinations of 120 and 135° protect the spine disc from compression and proffer more comfort for the users than other angles experimented. The adjustable sitting inclination SCRC is simple and affordable for low-income people with Spinal cord injury, especially for those in developing countries in order to support other therapies for their recovery processes.

Dyke–Davidoff–Masson syndrome (DDMS) is a rare, but important cause of drug-resistant seizures. Dyke–Davidoff–Masson syndrome is a constellation of clinical features that consists of hemiparesis, seizure, facial asymmetry, and intellectual disability with distinct neuroimaging features. A 27-year-old lady presented to us with drug-resistant epilepsy, hemiparesis, and intellectual disability that necessitated her withdrawal from school. Her brain magnetic resonance imaging (MRI) showed cerebral hemiatrophy, calvarial thickening, and hyperpneumatization of the frontal sinuses consistent with DDMS. We discuss the diagnostic and therapeutic implications of DDMS and advocate early referral and evaluation of people with epilepsy in sub-Saharan African settings.