e20748 Background: Osimertinib (+ chemotherapy) is the standard first-line treatment for EGFR -mutated non-squamous non-small cell lung cancer (NSqNSCLC). However, evidence regarding the efficacy of EGFR-TKI re-challenge after progression on osimertinib remains insufficient. This study evaluated the efficacy and safety of afatinib as a subsequent therapy following progression on osimertinib and conventional chemotherapy. Methods: This multicenter, single-arm, phase II study enrolled patients (pts) with advanced/recurrent EGFR -mutated (del19 or L858R) NSqNSCLC and an ECOG PS 0–1. All pts underwent NGS-based comprehensive genomic profiling (CGP) after progressing on osimertinib. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: Between Oct 2022 and Dec 2024, 19 pts were enrolled. Due to slow accrual, the study was terminated before reaching the planned sample size. Of 17 evaluable pts, the ORR was 11.8% (95% CI: 1.5-36.4), mPFS was 4.5 mos. (95% CI: 2.9-9.2), and mOS was 20.8 mos. (95% CI: 9.0-NA). CGP identified several biomarkers potentially involved in osimertinib resistance, including EGFR C797S (n = 1), ERBB2 mutation (n = 1), PIK3CA mutation (n = 1), RET mutation (n = 1), and METex14 skipping (n = 1); however, no clear correlation between these markers and afatinib efficacy was observed. Any-grade adverse events (AEs) occurred in 88.2% of pts, with Grade 3 AEs in 29.4% (5/17), primarily diarrhea, which were manageable with dose interruptions or reductions. Conclusions: Afatinib re-challenge showed limited efficacy in pts with EGFR -mutated NSqNSCLC pretreated with osimertinib and chemotherapy. While the safety profile was consistent with previous reports, these findings suggest that alternative therapeutic strategies should be prioritized in this clinical setting. (UMIN000049225). Clinical trial information: UMIN000049225 .

ABSTRACT Background Chemoimmunotherapy is widely used as the first‐line treatment for extensive‐stage small cell lung cancer (ES‐SCLC), but treatment options for second‐line have not changed. Amrubicin monotherapy is used as the standard treatment for relapsed SCLC, but since chemoimmunotherapy became an additional indication for ES‐SCLC, the efficacy and safety of second‐line amrubicin have not been sufficiently investigated. Methods We enrolled a total of 131 relapsed SCLC patients who received second‐line amrubicin at eleven institutions in Japan between August 2019 and June 2023. We retrospectively examined the efficacy and safety of second‐line amrubicin monotherapy. Results Twenty‐five (19.1%) and 106 patients (80.9%) had sensitive and refractory relapse, respectively. 51 (38.9%) and 80 (61.1%) patients received first‐line chemoimmunotherapy and first‐line chemotherapy, respectively. The median progression‐free survival (PFS) and overall survival (OS) were 3.6 months (95% confidence interval [CI], 3.1–4.1 months) and 7.9 months (95% CI, 6.7–9.1 months), respectively. The median PFS and OS were significantly longer in the sensitive group compared with the refractory group (PFS: 6.4 vs. 3.5 months, p = 0.008, OS: 9.4 vs. 6.4 months, p = 0.021, respectively). Treatment‐related adverse events were as follows: Grade 4 neutropenia in 51 patients (38.9%), grade 3 or higher febrile neutropenia in 18 patients (13.7%), and all grade interstitial lung disease in 13 patients (9.9%). Treatment‐related death was 1 patient (0.8%). Conclusion Second‐line amrubicin monotherapy for relapsed SCLC may be useful and well‐tolerated as a treatment option after first‐line chemoimmunotherapy or chemotherapy.

BACKGROUND:Chemoimmunotherapy is the standard first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC); however, a limited number of real-world cases meet the inclusion and exclusion criteria of clinical trials. This study investigated whether chemoimmunotherapy is selected in patients with ES-SCLC who meet eligibility criteria in real-world practice and identified their clinical characteristics. METHODS:A total of 198 patients diagnosed with ES-SCLC received first-line treatment at 11 institutions between August 2019 and June 2023. We evaluated the efficacy and safety of first-line treatment in patients meeting the eligibility criteria of the IMpower133 and CASPIAN trials. This multicenter retrospective study included 78 patients (39.4%) who met the eligibility criteria. RESULTS:Fifty-six (71.8%) and twenty-two (28.2%) underwent chemoimmunotherapy and chemotherapy, respectively. The proportion of patients aged ≥75 years was higher in the chemotherapy group. The median progression-free survival in the chemoimmunotherapy and chemotherapy groups was 5.1 versus 4.6 months (hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.29-0.84), respectively. The median overall survival in the chemoimmunotherapy and chemotherapy groups was 17.1 versus 9.4 months (HR 0.51; 95% CI, 0.29-0.88), respectively. The discontinuation rate of treatment-related adverse events did not differ significantly between the two groups (5.4% vs. 0.0%, p = 0.555). CONCLUSION:First-line chemoimmunotherapy is considered a valuable treatment option for patients with ES-SCLC who meet the eligibility criteria for clinical trials. However, even among eligible patients, chemotherapy alone may be selected based on various reasons, such as older age. Furthermore, a comprehensive analysis of real-world data is required. TRIAL REGISTRATION:This study was registered in the UMIN Clinical Trial Registry (A multicenter retrospective study to evaluate the efficacy and safety of platinum-based chemotherapy in combination with immunotherapy for extensive-stage small cell lung cancer in the real-world setting, UMIN000053134).

BACKGROUND:First-line combination therapy with anti-programmed cell death ligand 1 antibodies and platinum-based chemotherapy (chemoimmunotherapy) for extensive-disease small cell lung cancer (ED-SCLC) has been shown to be effective in clinical trials and widely used. Since the introduction of chemoimmunotherapy, very few studies have evaluated the treatment details and outcomes for patients with ED-SCLC in clinical settings. METHODS:We enrolled 181 ED-SCLC patients who received first-line chemotherapy or chemoimmunotherapy at 11 institutions in Japan between August 2019 and June 2023. We retrospectively investigated the characteristics and treatment regimens of patients with ED-SCLC who received first-line treatment. RESULTS:Ninety-six (53.0 %) and 85 (47.0 %) ED-SCLC patients received chemoimmunotherapy and chemotherapy, respectively. The proportions of older patients (≥75 years) and those with interstitial pneumonia were significantly higher in the chemotherapy group than in the chemoimmunotherapy group (age: 56.5 % vs. 28.1 %, p < 0.001; interstitial pneumonia: 41.2 % vs. 9.4 %, p < 0.001, respectively). The median overall survival in chemoimmunotherapy and chemotherapy groups were 15.0 and 9.7 months, respectively. The most common reasons for not selecting chemoimmunotherapy were interstitial pneumonia (34 patients,18.8 %), older age (27 patients, 14.9 %), and poor performance status (24 patients, 13.3 %). CONCLUSION:Although the efficacy of chemoimmunotherapy for patients with ED-SCLC has been suggested, only about half of the patients with ED-SCLC select chemoimmunotherapy, and there are various challenges in the treatment of ED-SCLC in clinical settings.

INTRODUCTION:Combination therapy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies and platinum-based chemotherapy has been widely used as a first-line treatment for patients with unresectable advanced non-small cell lung cancer (NSCLC) in clinical settings; however, prognostic biomarkers associated with survival outcomes have not been sufficiently investigated. METHODS:We enrolled 147 previously untreated patients with advanced NSCLC who were treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy at eight institutions in Nagano Prefecture between December 2018 and April 2023. We evaluated the prognostic value of the geriatric nutritional risk index (GNRI), a systemic inflammatory nutritional biomarker calculated from body weight and serum albumin level, for patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy. RESULTS:The cutoff value of the GNRI was set at 92. The high GNRI and low GNRI groups included 88 and 59 patients, respectively. The median follow-up period was 15.9 months. The overall survival (OS) in the high GNRI group was significantly longer than that in the low GNRI group (27.9 vs. 15.6 months, p = 0.015). Multivariate analysis revealed that a high GNRI was an independently favorable prognostic predictor for OS (hazard ratio, 1.73; 95% confidence interval, 1.06-2.86; p = 0.031). CONCLUSION:The present study demonstrates that the GNRI is a useful prognostic predictor in patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy in clinical settings.

Background: Rechallenge therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is known to confer some clinical benefit for patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). However, little is known about the efficacy of EGFR-TKI rechallenge after resistance to first-line (1L) osimertinib. This study aimed to assess the efficacy and safety of EGFR-TKI rechallenge therapy after resistance to 1L osimertinib in a Japanese clinical setting. Methods: Between April 2018 and August 2022, 26 patients who progressed after treatment with 1L osimertinib and received EGFR-TKI rechallenge were included in this multicenter retrospective analysis. Patients in whom 1L osimertinib was discontinued owing to toxicity and had subsequent disease progression were also included in the analysis. Results: Overall, the objective response rate for rechallenge therapy was 23.1%. The disease control rate was 53.9%, and the median progression-free survival (PFS) was 3.4 months. Patients who discontinued 1L osimertinib for toxicity had a higher response rate (42.9% vs. 15.8%) and longer PFS than those who discontinued it due to disease progression (median: 11.4 vs. 2.7 months, P = 0.001). Three patients (11.5%) developed rechallenge therapy-associated pneumonitis, two of which were grade >= 3. Conclusions: Rechallenge with EGFR-TKI after 1L osimertinib resistance showed limited clinical efficacy. However, it could be considered as a subsequent salvage therapeutic option for patients in whom 1L osimertinib was discontinued owing to toxicity.

INTRODUCTION:Chemoimmunotherapy is widely used as the first-line management of advanced non-small cell lung cancer (NSCLC) in clinical settings. However, predictive factors associated with the development of immune-related adverse events (irAEs) and prognostic factors for NSCLC patients undergoing chemoimmunotherapy remains largely unexplored. Therefore, in this study, we aimed to evaluate predictive factors for irAE development and prognostic factors associated with chemoimmunotherapy in NSCLC patients. METHODS:This study enrolled 199 patients with advanced and recurrent NSCLC who underwent chemoimmunotherapy across eight institutions in Nagano prefecture from December 2018 to January 2023. We examined predictive factors associated with irAE development and prognostic factors associated with overall survival (OS). RESULTS:Among the patients, 106 experienced irAEs, while 93 patients did not. A total of 44 (22.1%) patients developed multiple irAEs. High serum albumin levels (Alb >3.5 g/dL) emerged as an independent predictive factor associated with irAE development in logistic regression analysis (odds ratio; 2.35, 95% confidence interval 1.27-4.34, p = 0.007). Furthermore, the development of multiple irAEs (p = 0.016), lower lactate dehydrogenase level (<223 U/L, p = 0.002), and decreased neutrophil-to-lymphocyte ratio (<3, p = 0.049) were identified as independent favorable prognostic factors associated with OS in multivariate Cox hazard analyses. CONCLUSION:The study results suggest that high serum Alb is a predictive factor for irAE development and that the presence of multiple irAEs is a favorable prognostic indicator for NSCLC patients undergoing chemoimmunotherapy.

Background:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC) and contributed to the development of precision medicine. Osimertinib is a standard first-line (1L) treatment for EGFR-mutated NSCLC and has demonstrated superior survival benefits over previous-generation TKIs. However, resistance to osimertinib is nearly inevitable, and subsequent treatment strategies remain unmet medical needs in this setting. Afatinib, a second-generation EGFR-TKI, exhibits activity against certain uncommon EGFR mutation types in the 1L setting. There are a few case reports on the efficacy of afatinib against EGFR-dependent resistance after osimertinib treatment, although these have not been prospectively investigated.Methods:The present phase II, single-arm multicenter trial aims to verify the efficacy and safety of afatinib rechallenge after 1L osimertinib resistance. Patients (aged ≥20 years) with advanced or recurrent non-squamous NSCLC harboring drug-sensitive EGFR mutations (deletion of exon 19 or L858R) who were previously treated with 1L osimertinib and second-line chemotherapy other than TKIs are considered eligible. Undergoing next-generation sequence-based comprehensive genomic profiling is one of the key inclusion criteria. The primary endpoint is the objective response rate; the secondary endpoints are progression-free survival, overall survival, and tolerability. Thirty patients will be recruited in December 2023.Discussion:The results of this study may promote incorporating afatinib rechallenge into the treatment sequence after 1L osimertinib resistance, a setting in which concrete evidence has not been yet established.Registration:UMIN Clinical Trial Registry: UMIN000049225.

Introduction. We prospectively examined current clinical practices in patients with inoperable epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) fusion-positive (EGFR+ and ALK+, respectively) non-small cell lung cancer (NSCLC) in Nagano Prefecture, Japan.Material and methods. The study population consisted of newly diagnosed patients with inoperable EGFR+ and ALK+ NSCLC in 14 hospitals in Nagano between May 2016 and March 2019. Both initial and subsequent treatment decisions were made at the discretion of the attending physician.Results. A total of 281 patients with EGFR+ NSCLC (mean age, 74 years, 59.1% female) and 26 patients with ALK+ NSCLC (mean age, 66 years, 53.8% female) were included in the study. The study population consisted of 148/107/29/20/3 cases with performance status 0/1/2/3/4 and 6/2/31/194/75 cases with clinical stage I/II/III/IV/recurrence, respectively. First-line therapy with tyrosine kinase inhibitors was performed in 259 (92.2%) and 22 (84.6%) patients with EGFR+ and ALK+ NSCLC, respectively. The median overall survival rate was 41.2 months (95% CI 36.8-45.6 months) with EGFR+. It was not reached with ALK+ .Conclusions. This observational analysis represents a valuable resource for evaluating the outcomes of treatment in patients with NSCLC.

Treatment of synchronous multiple primary cancers is clinically difficult. We report four cases of synchronous primary cancers, including advanced and metastatic non-small cell lung cancer (NSCLCs) highly positive for programmed death ligand-1 (PD-L1) expression and initially treated with pembrolizumab. Pembrolizumab was efficacious in 2 patients with NSCLC lesions, followed by chemoradiotherapy for esophageal cancer (case 1) and chemotherapy for gastric cancer (case 2). Both cancers in case 1 showed a complete response for 3 years, while progression of the accompanying gastric cancer resulted in mortality at 20 months in case 2. Both NSCLC and gastric cancer in case 3 failed to respond to pembrolizumab, but the accompanying laryngeal cancer in case 4 showed a complete response, and cytotoxic chemotherapy for NSCLC was continued for 18.0 months. Our clinical experience suggests that pembrolizumab is a useful therapeutic approach for patients with synchronous cancers, including NSCLC that highly expresses PD-L1.

Introduction: Combination immunotherapy is widely used in clinical practice as the first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, predictive factors associated with long-term response to combination immunotherapy have not been well investigated. Herein, we compared the clinical findings, including systemic inflammatory nutritional biomarkers, between responders and nonresponders to combination immunotherapy. In addition, we investigated the predictive factors associated with long-term response to combination immunotherapy. Methods: This study included a total of 112 previously untreated advanced NSCLC patients who received combination immunotherapy at eight institutions in Nagano prefecture between December 2018 and April 2021. The responders were defined as those who achieved progression-free survival for 9 months or longer with combined immunotherapy. We evaluated predictive factors associated with long-term response, and the favorable prognostic predictors associated with overall survival (OS) using statistical analyses. Results: The responder and nonresponder groups included 54 and 58 patients, respectively. Compared with the nonresponder group, the responder group had significantly younger age (p = 0.046), higher prognostic nutritional index (44.8 vs. 40.7, p = 0.010), lower C-reactive protein/albumin ratio (CAR) (0.17 vs. 0.67, p = 0.001), and a higher rate of complete plus partial response (83.3% vs. 34.5%, p < 0.001). The area under the curve and optimal cut-off value for CAR were 0.691 and 0.215, respectively. The CAR and best objective response were identified as independent favorable prognostic predictors associated with OS in the multivariate analyses. Conclusion: The CAR and best objective response were suggested to be useful predictors of long-term response in NSCLC patients who received combination immunotherapy.

Abstract Background Combination immunotherapy (immune checkpoint inhibitors and cytotoxic anticancer agents) is widely used as first‐line treatment for advanced non‐small cell lung cancer (NSCLC). However, the therapeutic effect of combination immunotherapy has not been fully investigated. C‐reactive protein, performance status, lactate dehydrogenase, albumin, and derived neutrophil‐to‐lymphocyte ratio (C‐PLAN) are useful biomarkers for predicting the prognosis of NSCLC; however, there are no reports examining the C‐PLAN index, which combines these five factors in a single prognostic factor. Methods We retrospectively collected data from 178 patients with previously untreated advanced NSCLC who received combination immunotherapy at multicenter institutions in Nagano Prefecture between December 2018 and April 2022. We investigated the utility of the C‐PLAN index as a prognostic factor using Cox regression analysis and correlated it with survival. Results The good and poor C‐PLAN index groups included 85 and 93 patients, respectively. The good C‐PLAN index group had a longer median progression‐free survival (PFS) (10.7 vs. 6.0 months; p = 0.022) and overall survival (OS) (25.3 vs. 16.5 months; p = 0.003) than the poor C‐PLAN index group. The C‐PLAN index was an independent favorable prognostic factor that correlated with PFS and OS in multivariate analysis. The good C‐PLAN index group had a higher proportion of never‐smokers (16.5 vs. 4.3%; p = 0.007) and stage III disease/postoperative recurrence (32.9 vs. 15.1%; p = 0.005) than the poor C‐PLAN index group. Conclusion The C‐PLAN index is a useful prognostic factor for patients with previously untreated advanced NSCLC undergoing combination immunotherapy.

As the COVID-19 pandemic persists, pregnant women have been increasingly affected worldwide. Women during the last trimester of pregnancy are susceptible to severe COVID-19, and there are many challenges towards its treatment. Monoclonal antibody treatment (MAT) is approved for COVID-19 patients to reduce disease severity. However, there are few reports on the MAT in perinatal women. Herein, we report a 39-year-old pregnant female (36 weeks and 6 days of gestation) with improvement in COVID-19 pneumonia after treatment with casiribimab/ imdevimab, resulting in successful vaginal delivery (a 2.868 kg male newborn), along with a literature review. Early diagnosis and treatment of pregnant women with COVID-19 are important. Infectious diseases doctors and/ or obstetricians should be aware of the MAT option administered to perinatal COVID-19 women to reduce disease severity.

Background: There is an increasing incidence of Pneumocystis pneumonia among individuals without the human immunode�ciency virus (HIV) infection (non-HIV Pneumocystis pneumonia). However, the prognostic factors for patients with non-HIV Pneumocystis pneumonia have not been identi�ed. Moreover, A-DROP (for classifying the severity of community-acquired pneumonia) or the blood urea nitrogen-to-serum albumin ratio, which is reported to be predictor of mortality of community-acquired pneumonia, has not been established as an e�cient prognostic factor in patients with non-HIV Pneumocystis pneumonia. In this study, we analyzed the prognostic factors for non-HIV Pneumocystis pneumonia and evaluated the effectiveness of A-DROP and the blood urea nitrogen-to-serum albumin ratio as prognostic factors. Methods: This retrospective study involved a chart review of the medical records of 102 patients diagnosed with non-HIV Pneumocystis pneumonia between January 2003 and May 2019 at �ve medical facilities. Prognostic factors associated with the 30-day mortality were assessed using multiple logistic regression analysis. Results: Among the 102 patients with non-HIV Pneumocystis pneumonia, 46 (45.1%) had autoimmune diseases, 19 (18.6%) had hematological malignancies, 18 (17.7%) had solid malignancies, and 19 (18.6%) had other diseases. The 30-day mortality rate for non-HIV Pneumocystis pneumonia was 20.5% in this study population. Compared with survivors, non-survivors had signi�cantly lower serum albumin levels and a signi�cantly higher age, corticosteroid dosage at the onset of Pneumocystis pneumonia, alveolar–arterial oxygen gradient, A-DROP score, lactate dehydrogenase levels, blood urea nitrogen levels, and blood urea nitrogen-to-serum albumin ratio. The results of multivariate analysis showed that a high A-DROP score and blood urea nitrogen-to-serum albumin ratio at treatment initiation were signi�cantly associated with the 30-day mortality risk. Conclusions: A high A-DROP Abbreviations: PcP; Pneumocystis pneumonia, invasive positive pressure

INTRODUCTION:Risk factors for seriously ill coronavirus disease 19 (COVID-19) patients have been reported in several studies. However, to date, few studies have reported simple risk assessment tools for distinguishing patients becoming severely ill after initial diagnosis. Hence, this study aimed to develop a simple clinical risk nomogram predicting oxygenation risk in patients with COVID-19 at the first triage.METHODS:This retrospective study involved a chart review of the medical records of 84 patients diagnosed with COVID-19 between February 2020 and March 2021 at ten medical facilities. The patients were divided into requiring no oxygen therapy (non-severe group) and requiring oxygen therapy (severe group). Patient characteristics were compared between the two groups. We utilized univariate logistic regression analysis to confirm determinants of high risks of requiring oxygen therapy in patients with moderate COVID-19.RESULTS:Thirty-five patients ware in severe group and forty-nine patients were in non-severe group. In comparison with patients in the non-severe group, patients in the severe group were significantly older with higher body mass index (BMI), and had a history of hypertension and diabetes. Serum blood urea nitrogen (BUN), lactic acid dehydrogenase (LDH), and C-reactive protein (CRP) levels were significantly higher in the severe group. Multivariate analysis showed that older age, higher BMI, and higher BUN levels were significantly associated with oxygen requirements.CONCLUSIONS:This study demonstrated that age, BMI, and BUN were independent risk factors in the moderate-to-severe COVID-19 group. Elderly patients with higher BMI and BUN require close monitoring and early treatment initiation.

Fanconi anemia (FA) is characterized clinically by bone marrow failure, congenital malformations, sensitivity to DNA cross-linking agents, and increased risk of malignancy. Hematological cancer is the best-described malignancy in patients with FA, but the susceptibility to the development of solid tumors is also well documented, especially after hematopoietic stem cell transplantation (HSCT). With regard to the development of solid tumors in patients with FA, head and neck, esophageal, and anal squamous cell carcinoma are well known, but reports of lung cancer are extremely rare. Here, we describe an FA patient with a history of HSCT that developed 3 serial cancers – oral, esophageal, and nonsmall cell lung cancer – over a period of 6 years. The third lesion was nonsmall cell lung cancer and its location corresponded closely to the field of irradiation treatment for prior esophageal cancer. The occurrence of lung cancer in patients with FA is uncommon, but FA patients should be screened regularly and serially. Our case also indicated the importance of the irradiated field as a location for subsequent cancer development.

Background: There is an increasing incidence of Pneumocystis pneumonia among individuals without the human immunodeficiency virus (HIV) infection (non-HIV Pneumocystis pneumonia). However, the prognostic factors for patients with non-HIV Pneumocystis pneumonia have not been identified. Moreover, A-DROP (for classifying the severity of community-acquired pneumonia) or the blood urea nitrogen-to-serum albumin ratio, which is reported to be predictor of mortality of community-acquired pneumonia, has not been established as an efficient prognostic factor in patients with non-HIV Pneumocystis pneumonia. In this study, we analyzed the prognostic factors for non-HIV Pneumocystis pneumonia and evaluated the effectiveness of A-DROP and the blood urea nitrogen-to-serum albumin ratio as prognostic factors. Methods: This retrospective study involved a chart review of the medical records of 102 patients diagnosed with non-HIV Pneumocystis pneumonia between January 2003 and May 2019 at five medical facilities. Prognostic factors associated with the 30-day mortality were assessed using multiple logistic regression analysis. Results: Among the 102 patients with non-HIV Pneumocystis pneumonia, 46 (45.1%) had autoimmune diseases, 19 (18.6%) had hematological malignancies, 18 (17.7%) had solid malignancies, and 19 (18.6%) had other diseases. The 30-day mortality rate for non-HIV Pneumocystis pneumonia was 20.5% in this study population. Compared with survivors, non-survivors had significantly lower serum albumin levels and a significantly higher age, corticosteroid dosage at the onset of Pneumocystis pneumonia, alveolar–arterial oxygen gradient, A-DROP score, lactate dehydrogenase levels, blood urea nitrogen levels, and blood urea nitrogen-to-serum albumin ratio. The results of multivariate analysis showed that a high A-DROP score and blood urea nitrogen-to-serum albumin ratio at treatment initiation were significantly associated with the 30-day mortality risk. Conclusions: A high A-DROP score and blood urea nitrogen-to-serum albumin ratio at treatment initiation are independent prognostic predictors of mortality risk in patients with non-HIV Pneumocystis pneumonia.

Background & Aims: Favipiravir is approved in India for mildmoderate COVID-19.We aimed to observe effectiveness & safety of favipiravir in mild COVID-19 in real world setting.Methods: Retrospective cohort study was conducted in favipiravir treated mild COVID-19 patients(SpO 2 ≥94) at 4 Indian centres after ethics committee approval.Medical records from Oct 2020 -Feb 2021 were analyzed to capture required details.Results: 283 mild COVID-19 patients received favipiravir.Mean age was 50.5AE16.7years, M:F =1.4:1.51.6% had co-morbidities, with hypertension (40%) and diabetes (35.7%) as frequent ones.26.1% had multiple (≥2) co-morbidities.Mean SpO 2 & RR at baseline was 96.9 AE 1.5% & 21.5 AE 12/min respectively.Overall CRP (30.3AE46.3),d-Dimer (433.5AE746.4),serum ferritin (321.8AE329.5 and LDH (234.4AE99.7)were raised at baseline.Fever (90.8%), cough (59.4%), myalgia (32.5%) and fatigue (30.4%) were common presenting symptoms.55.1% required hospitalization.Favipiravir was prescribed for median duration of 14 days.12.4% received systemic steroids.Fever resolution occurred in median duration of 4 days(1-10 d).Fever resolved in 86.2% and 90.8% by day 7 and 10.Median time to clinical cure was 5 days (1-13 days).Clinical cure rate at day 7, 10 and 14 was 79.2%, 90.5% and 94.7%.At Baseline 47 (16.6%) patients were on respiratory support which reduced from day 3 (n=34) (12%) to day 14 (n=2) (0.7%).(n=15) 5.3% had disease progression with mortality in 2. TEAEs were observed in (n=23)8.1%.Elevation of liver transaminases 14 (5%), loose motion 5 (1.8%) were most frequent TEAEs.Conclusion: Favipiravir was found effective in majority of mild COVID-19 patients despite high risk association.It was well tolerated and no new safety signals were detected.

We report a fulminant case of classical Hodgkin lymphoma (CHL). The patient died only approximately 2 months after the onset of subjective symptoms. Autopsy specimens revealed atypical cells resembling Hodgkin and Reed-Sternberg (HRS) cells in a rich inflammatory background in various organs. There were marked, characteristic angiodestructive lesions from infiltrating HRS-like cells and numerous macrophages. The HRS-like cells were infected with Epstein-Barr virus (EBV), immunohistochemically positive for PAX5 and CD30, and negative for CD3, CD20, and ALK. Most B-cell markers other than PAX5 were negative, and the HRS-like cells also expressed cytotoxic molecules. Monoclonal rearrangement of immunoglobulin heavy chain was detected by PCR analysis. According to the 2016 WHO classification, we diagnosed mixed cellularity CHL. However, EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified and EBV-positive B-cell lymphoma, unclassifiable with features intermediate between DLBCL and CHL were considered as differential diagnoses because both tumors are aggressive EBV-positive large B-cell neoplasms with reactive inflammatory cells and sometimes contains HRS-like cells. The clinical condition of the current case was closer to these two entities than to CHL. A diagnosis of EBV-positive large B-cell neoplasms was difficult because of overlapping morphological and immunohistochemical characteristics, but should be considered for prognosis.

We present the case of a 74-year-old Japanese woman who presented with dyspnea, a palpable right breast mass, and swollen right axillary lymph node. Imaging studies revealed bilateral pleural effusion and systemic lymph adenopathy and pleural fluid study showed high levels of triglycerides. A right inguinal lymph node biopsy disclosed malignant lymphoma cells that were human T-cell leukemia virus type 1 (HTLV-1) provirus DNA-positive, a condition endemic to patient's birthplace, by the Southern blot hybridization method. She was diagnosed as having adult T-cell leukemia/lymphoma (ATL) with chylothorax. After commencing chemotherapy for ATL, her chylothorax disappeared and swollen lymph nodes reduced remarkably, indicating an association between the chylothorax and ATL. Bilateral chylothorax is a relatively rare condition associated with such nontraumatic causes as ATL. Clinicians should therefore bear chylothorax in mind when encountering patients with pleural effusion. A detailed medical history can also enable prompt diagnosis and appropriate treatment.