Nivolumab in Recurrent/Metastatic Squamous Cell Carcinoma of Head and Neck: A Tertiary Cancer Center Experience

Background Immunotherapy is a proven therapeutic option in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum therapy. At present, there are no published Indian data regarding administration of nivolumab in this setting. Aim The aim of this study is to retrospectively evaluate the efficacy and toxicity of nivolumab in R/M HNSCC among Indian patients who progressed after one or more lines of chemotherapy, including platinum agents. Methods All patients of R/M HNSCC who received nivolumab between 2/6/2018 to 31/3/2020 were assessed retrospectively for the efficacy and toxicity of nivolumab therapy. Statistical Analysis All the data analysis was performed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA). Descriptive analysis was performed to obtain baseline characteristic of the study sample. Survival analysis was done using the Kaplan–Meier method. Results Nivolumab therapy was tolerated well, with no new safety concerns, except one (8.3%) patient experienced grade ¾ toxicity (gastrointestinal). The clinical benefit rate (CBR) was found to be 66.7%. The median progression-free survival (PFS) was 3 months (95% CI; 2.093–3.907), and median overall survival (OS) was 8 months (95% CI; 3.731–12.269) from the date of first dose of nivolumab. Conclusions In our study, efficacy and toxicity were comparable with international data with no new safety concerns. Nivolumab emerged as an astonishing treatment option with tolerable toxicity profile in patients with R/M HNSCC postplatinum therapy, although limited treatment options are available at present.

442 Thrombocytopenia following transcatheter aortic valve implantation in portico and Evolute recipients

Aims Thrombocytopenia (TP) following transcatheter aortic valve implantation (TAVI) is a common phenomenon and is associated with mortality and complications. The underlying mechanisms are still unclear. Few data exist on differential risk of thrombocytopenia between different types of transcatheter valves. Methods and results This retrospective study aimed to evaluate the different behaviour of platelet count in Portico or Evolut recipients. Patients underwent TAVI between Feb 2017 to Aug 2021 at Gemelli Molise Hospital were enrolled and were divided in two groups: Portico (n = 90) and Evolut recipients (n = 64). Blood samples and platelets count were collected at admission (T1), implantation day (T2), second post TAVI day (T3), third post TAVI day (T4) and at discharge (T5). Drop platelets count (DPC) was calculated in this way: 100% × (baseline platelet count–nadir platelet count)/(baseline platelet count). CT and echo data were collected. The overall analysis consisted of a total of 154 patients who underwent TAVI. Among these patients, 90 patients (58%) were implanted with Portico valve, and 64 patients (42%) with an Evolut valve. We observed no differences among baseline characteristic between two groups. Interestingly, patients implanted with Portico valve, showed a high degree of thrombocytopenia at time T3, T4 and T5 (respectively, 122 ± 42 vs. 143 ± 43, P 0.004; 111 ± 39 vs. 137 ± 43, P 0.000; 136 ± 56 vs. 173 ± 69, P 0.001). DPC was greater in Portico valve (44 ± 16 vs. 31 ± 15, P = 0.000). No differences were found among inflammation variables (neutrophil lymphocyte ratio, CRP), implantation depth, degree of calcification evaluated with CT (FACTS score) and PVL. Balloon post dilatation (BPD) was performed in 33% of Portico recipients vs. 18% of Evolut recipients (P 0.044). No correlations were found between DPC and BPD in Portico patients (r = 0.035, P = 0.744) and Evolut recipients (r = 0.074, P = 0.569). Conclusions Our study suggests a more thrombocytopenia in Portico recipients, irrespective inflammation, valve calcification, perivalvular leak, implantation factors. Larger studies are needed to confirm these data.

Clinical outcomes in stage III non-small cell lung cancer patients treated with durvalumab after sequential or concurrent platinum-based chemoradiotherapy – single institute experience

Background Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the usage of gemcitabine. Patients and methods We retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treatment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients. Results Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during concurrent treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%). Conclusions Our survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.

455. Diagnostic Value of Hematological Parameters in Different Stages of the Disease in Covid-19 Patients

Background COVID-19 infection is associated in some individuals with a rapid onset of systemic proinflammatory state leading to cytokine storm followed by multisystem organ failure. We are interested in studying the prognostic value of complete blood count parameters in different stages of the diseases based on the serology. Methods This is a retrospective cohort study of patients with confirmed COVID-19 admitted to our hospital between 10/1/2020 to 2/28/2021. Study individuals had complete CBC profile and COVID-19 serology with well-defined clinical outcome (discharged alive or expired). They were divided in 3 groups based on serology results: group 1 (early disease) had no antibodies, group 2 (immune phase) had + IgM, and group 3 (late phase) had only + IgG. Demographic, clinical and laboratory data were reviewed. Simple t-test was used for continuous variables and chi-square test was used for categorical variables. Anova test was used to compare the difference across multiple groups. GraphPad PRISM was used for all analysis. Results A total of 202 confirmed covid 19 cases were included in the study. There was no difference between the 3 groups in terms of age, gender, and body mass index (BMI). We did observe an increase in incidence in Latinx (group 1, 34%; group 2, 51%; group 3, 38%). Hypertension and diabetes were major co-morbidities in these patients. Absolute neutrophil count (ANC) and platelet count (PC) showed significant changes across the 3 groups: mean ANC for group 1, 4.868 (SD 3.117); group 2, mean 6.951 (SD 3.843); and group 3 mean 5.59 (SD 3.236). PC in group 1 mean 193.2 (SD 90.25); group 2 mean 271.1 (SD 143.4); and group 3 mean 228.6 (SD 75.33) p-value 0.0008. The difference can be seen in the derived monocyte platelet rationMPR, neutrophil lymphocyte ratio NLR, platelet lymphocyte ratio PLR and aggregate index of systemic inflammation AISI values and they tend to be higher in group 2 (MPR p-value 0.0067, NLR p-value 0.0123, PLR p-value 0.0294, AISI p-value of 0.0190). Baseline characteristic CBC parameters Conclusion The study demonstrates that MPR, NLR, PLR and AISI have a potential role in categorizing the disease stage based on only CBC profiling.Properly designed prospective studies with a larger sample size should be performed to confirm the disease stratification ability of derived CBC indices like MPR, NLR, PLR and AISI. Disclosures All Authors: No reported disclosures

Heart Rate Recovery in Adult Individuals with Asthma

Background. Slow heart rate recovery (HRR) after exercise is predictor of overall mortality in individuals with and without cardiovascular or respiratory disorders. No data on adults with asthma are available. Aim. To evaluate the prevalence of slow HRR in these individuals as compared with those with chronic obstructive pulmonary disease (COPD).Methods. Retrospective analysis of baseline characteristics and physiological response to the six-minute walking distance test of stable individuals with asthma or COPD. Slow HRR was defined as HRpeak - HR at 1 minute after end exercise < 12 bpm.Results. Individuals with asthma walked significantly longer (median (IQR): 455 (385-512) vs 427 (345-485) meters; p= 0.005) with a lower prevalence of slow HRR (30.3% vs 49.0%, respectively: p<0.001) than those with COPD. Individuals with asthma and slow HRR were older and walked less than those with normal HRR, without any difference in airway obstruction or in disease severity. Multivariate analysis showed that only the difference HRpeak - baseline HR (∆HR), was predictor of slow HRR in both groups.Conclusion. More than 30% of adult individuals with asthma may show slow HRR. Only exercise ∆HR but no baseline characteristic seems predict the occurrence of slow HRR.

Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn’s disease: a Chinese real-world study

Background Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn’s disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure–response relationship in CD treatment in the real-world setting. Methods We retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn’s disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn’s disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis. Results Nineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 μg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 μg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02). Conclusions UST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 μg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021).

Diabetes Mellitus as a Risk Factor for Drug Resistance Tuberculosis: A Retrospective Cohort Study at King Abdul Aziz University, Jeddah

Background: The association between tuberculosis (TB) and diabetes mellitus (DM) is re-emerging with the epidemic of type II diabetes. Both TB and DM were of the top 10 causes of death.[1] This study explores diabetes mellitus as a risk factor for developing the different antitubercular drug-resistant (DR) patterns among TB patients. Methods: A retrospective cohort study has been conducted on all TB cases reported to the King Abdul Aziz University Hospital, Jeddah, between January 2012 to January 2021. All culture-confirmed and PCR-positive TB cases were included in this study. Categorical baseline characteristic of TB patient has been compared with DM status by using Fisher's exact and Pearson chi-square test. The univariable and multivariable logistic regression model was used to estimate the association between DM and different drug resistance patterns. Results: Of the total 695 diagnosed TB patients, 92 (13.24%) are resistant to 1st line anti TB drugs. Among 92 DR-TB patients, 36 (39.13%) are diabetic. The percentage of different patterns of DR-TB with DM, in the case of mono DR (12.09%), poly DR (4.19%) MDR (0.547%). As a risk factor, DM has a significant association with DR-TB, mono drug-resistant, and pyrazinamide-resistant TB (P-value <0.05). The MDR and PDR separately do not show any significant association with DM, but for further analysis, it shows a significant association with DM when we combined. Conclusion: Our study identified diabetes mellitus as a risk factor for developing DR-TB. Better management of DM and TB infection caring programs among DM patients might improve TB control and prevent DR-TB development in KSA.

Effectiveness and safety of edoxaban in atrial fibrillation patients from the ETNA-AF global registry

Background/Introduction ETNA-AF (ETNA) is a multinational, prospective, observational study evaluating the experience with edoxaban in the clinical practice of patients with atrial fibrillation (AF). ENGAGE AF-TIMI 48 was a randomized double-blind trial that tested the clinical benefits of edoxaban versus warfarin. The recommended dose is 60 mg, dose-reduced to 30 mg daily in patients with at least 1 of 3 label-indicated criteria (renal impairment [creatinine clearance: 15–≤50 mL/min], weight ≤60 kg, or concomitant use of potent P-glycoprotein inhibitors). Purpose We assessed whether the effectiveness and safety of edoxaban in clinical practice were consistent with findings from the pivotal randomized clinical trial. Methods We obtained patient-level data from ETNA and ENGAGE AF-TIMI 48. We initially extracted patients from similar geographic regions, and then used propensity-score matching (PSM) to adjust key baseline characteristic differences between studies. The primary effectiveness endpoint was all stroke or systemic embolism (SSE) and mortality; the safety endpoint was major bleeding (MB). We used Cox proportional hazards models to compare event rates for the clinical outcomes between ETNA and ENGAGE AF-TIMI 48. Results 8,615 AF patients with CHADS2 score ≥2 received the 60 mg edoxaban recommended dose (5,462 ETNA; 3,153 ENGAGE AF-TIMI 48). After PSM, key baseline characteristics were well-balanced between the studies: mean age 71.0 years (SD: 9.07); for both ETNA and ENGAGE AF-TIMI 48 median CHA2DS2-VASc score and median HAS-BLED score were 4 and 2. The annualized incidence rate of SSE was 1.65% in ETNA vs 1.53% in ENGAGE AF-TIMI 48 (HR 0.98; 95% CI 0.49, 1.93; p=0.94). ETNA had similar annualized mortality, 2.81%, compared with ENGAGE AF-TIMI 48, 2.34%, (HR 1.49; 95% CI 0.84, 2.63; p=0.17). MB was less frequent in ETNA vs ENGAGE AF-TIMI 48 (1.10% vs 3.56%; HR 0.25; 95% CI 0.14, 0.44; p&lt;0.05). Findings were similar for the recommended 30 mg edoxaban reduced dose. Conclusions The effectiveness of edoxaban in clinical practice from a large registry was consistent with efficacy findings from the randomized controlled trial. We observed a lower rate of bleeding events in the ETNA observational study compared with the ENGAGE AF-TIMI 48 trial. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was sponsored by Daiichi Sankyo Inc.

Proposal for Modifications to the Bangkok Urban Health System that would Improve the Quality of Health, Independent Living, and Maintenance of Older Adults with Fall-related Trauma (Bangkok Falls Study)

BackgroundThe Bangkok falls study aimed to identify fall-associated factors, including home healthcare hazards, nutritional status, hydration status, sarcopenia, frailty, locomotive syndrome, and health status of urban older adults in a middle-income country.Methods This was a population-based cohort study that enrolled adults who lived in Bangkok, Thailand. Our study recruited older adults aged ≥ 60 years old, able to walk, and expected to live in the community for at least 2 years. The study had three phases included; phase 1: subject identification and terminology clarification. Phase 2: we collected data at community sites on baseline characteristic and fall risk identification. Examinations and laboratory investigations were scheduled for one month later. Phase 3: telephone follow up for falls rate, functional status and death at 3, 6, 12 months.Results A total 1,001(51.84%) people were enrolled for our study. The average age of our study was 69.9 years old (SD, 6.8), and two-thirds were female. Using “Stopping Elderly Accidents, Death and Injuries” (STEADI) screening fall risk, our study found that 37.7% had scores ≥ 4, which means that there is a risk of fall. In addition, the risk of falls increased among older adults aged 75–84 years (49.5%) and older adults aged ≥ 85 years (67.7%) (P-value < 0.001).ConclusionThis study demonstrated the feasibility of conducting a population-based cohort study among urban older adults in a middle-income country using the local community healthcare system. Our study have a tendency to provide data source for fall risk factors and disability in older adults.

New York Heart Association Functional Class correlated with Depression: Study in Saiful Anwar Hospital

Background: Heart Failure prevalence was raising as one of the most Objective: to find the correlation of New York Heart Association Functional Class in heart failure patient with Depression Method: This cross-sectional study recruited 342 patients diagnosed with HF with previously for more than 3 months, at dr. Saiful Anwar General Hospital during December 2016 to March 2021. Each patient was interviewed for their demography data, and their clinical data, and assessed for their depression with Montgomery-Asberg Depression Rating Scale for Indonesian version. We used Spearman coefficients (rs) to evaluate the correlations between variables. Results: Baseline characteristic among depression and non-depression group demonstrated no significant difference (p>0.05), but for marital status. Populations was predominantly male, with ACE-i/ARB and Beta-blockers treatment. Non predominant treatment was MRAs, Diuretics, Digoxin. Baseline age was 22 years old until 87 years old. Baseline LVEF was 50.4±12.9%. (p >0.05). There were significant correlations between NYHA Class and marital status (p < 0.05), while the other baseline was not significantly different. We performed log regression for the confounding. The result was NYHA Class significantly correlated with and effects the depression. Conclusion: In heart failure patients, NYHA Class was significantly correlated with depression.