Fatal hemophagocytic lymphohistiocytosis with intravascular large B-cell lymphoma following coronavirus disease 2019 vaccination in a patient with systemic lupus erythematosus: an intertwined case.

Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a rare adverse event following the coronavirus disease 2019 (COVID-19) vaccination. We report a case of neuropsychiatric symptoms and refractory HLH in a woman with systemic lupus erythematosus (SLE) after receiving her COVID-19 vaccine treated with belimumab, later found to have intravascular large B-cell lymphoma (IVLBCL) at autopsy. A 61-year-old woman with SLE was referred to our hospital because of impaired consciousness and fever. One month prior to consulting, she received her second COVID-19 vaccine dose. Afterward, her consciousness level decreased, and she developed a high fever. She tested negative for SARS-CoV-2. Neuropsychiatric SLE was suspected; therefore, glucocorticoid pulse therapy was initiated on day 1 and 8. She had thrombocytopenia, increased serum ferritin levels and hemophagocytosis. The patient was diagnosed with HLH and treated with etoposide, dexamethasone and cyclosporine. Despite treatment, the patient died on day 75; autopsy report findings suggested IVLBCL as the underlying cause of HLH. Differentiating comorbid conditions remains difficult; however, in the case of an atypical clinical presentation, other causes should be considered. Therefore, we speculate that the COVID-19 vaccination and her autoimmune condition may have expedited IVLBCL development.

Disease control in patients with non-small cell lung cancer using pemetrexed: Investigating the best treatment strategy.

BACKGROUND: Pemetrexed (PEM) is the primary chemotherapy for non-small cell lung cancer (NSCLC), showing potential for long-term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches. METHODS: A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not. RESULTS: Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor-1 (TTF-1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p < 0.001). CONCLUSIONS: Our findings indicated that maintaining the dose of PEM after the second treatment cycle in patients with NSCLC, along with concurrent use of Bev and the presence of TTF-1 positivity, could enhance disease control rates and extend survival.

Investigation of response of patients with non-small cell lung cancer to docetaxel (plus ramucirumab) therapy in second-line treatment.

BACKGROUND: Several options for second-line therapy are available for patients with advanced non-small cell lung cancer (NSCLC); however, the optimal therapy remains unclear. Docetaxel (DTX) monotherapy and DTX plus ramucirumab (RAM) are the recommended second-line treatment options. However, the efficacy of these treatments remains unsatisfactory. The aim of this study was to identify the clinical characteristics of patients with NSCLC who respond to DTX or DTX + RAM and factors that predict response. METHODS: Patients with NSCLC treated with DTX or DTX + RAM after second-line therapy were retrospectively analyzed. Patients were compared with those who responded or did not respond to the post-treatment efficacy assessment. RESULTS: Of 53 patients, 12 (22.6%) had lung cancer that responded to DTX or DTX + RAM therapy (response group). Multivariate analysis identified the absence of immune checkpoint inhibitors (ICIs) in the immediate prior therapy and a reduced dose of DTX after the second cycle as significant independent risk factors predicting nonresponse to DTX and DTX + RAM therapy in patients with NSCLC. The overall survival was significantly longer in the response group compared to the nonresponse group (p = 0.016). CONCLUSIONS: Our results suggest that DTX and DTX + RAM therapies immediately after treatment with ICI-containing regimens as well as continuation of DTX without dose reduction after the second cycle may increase the response rate and prolong survival in patients with NSCLC.

Investigation of response factors for monotherapy with immune checkpoint inhibitors in non-small cell lung cancer patients with PD-L1 expression <50.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is currently approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with programmed death ligand-1 (PD-L1) expression ≥50%. However, the efficacy of ICI monotherapy in patients with PD-L1 expression <50% has not yet been fully elucidated. The aim of this study was to identify the clinical characteristics of NSCLC patients with PD-L1 expression <50% who respond to single-agent ICIs and factors that predict response. METHODS: Patients with advanced or recurrent NSCLC with a PD-L1 tumor proportion score (TPS) of 50% or less who received new monotherapy with an ICI between July 2012 and December 2022 were retrospectively analyzed. Patients with response were compared with those without response in the post-treatment response assessment. RESULTS: Among the 37 patients, six (16.2%) NSCLC patients in the response group responded to ICI monotherapy and had a significantly lower body mass index (BMI) (p = 0.003). Significantly more patients in the response group developed immune-related adverse events (irAEs) than in the nonresponse group (p < 0.001). Multivariate analysis identified high BMI as a significant independent risk factor predicting nonresponse to ICI monotherapy in NSCLC patients with PD-L1 < 50%. CONCLUSIONS: Among NSCLC patients with PD-L1 < 50%, those with a higher BMI were more likely to be nonresponders to ICI monotherapy. In addition, the group that responded to ICI monotherapy may have been at higher risk of developing irAEs, suggesting that careful follow-up is warranted.

Influencing factors of efficacy and long-term use of amrubicin in patients with small cell lung cancer.

BACKGROUND: Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy. METHODS: The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group). RESULTS: The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001). CONCLUSIONS: In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival.

Differential response in patients with large cell neuroendocrine carcinoma of the lung to initial therapy: A case series.

BACKGROUND: Large cell neuroendocrine tumors of the lung (LCNEC) are rare. Chemotherapy with the small cell lung carcinoma (SCLC) regimen is the most appropriate treatment for LCNEC. However, there is evidence that the non-small cell lung cancer regimen is also effective in some reported cases. Due to the differences in response to LCNEC treatment, a standard of care for LCNEC has not been established. CASES: The clinical records of nine patients with LCNEC who were treated with anticancer drugs based on an SCLC regimen from March 2016 to March 2022 were retrospectively reviewed. The patients who responded to treatment after one cycle of systemic chemotherapy were compared to those who did not respond. All patients in the responder group had a performance status (PS) of 0 or 1. However, 5 of the 6 patients in the non-responder group had a PS of 2 or 3, indicating that many patients were in poor general condition. Although patients with multiple metastases to more than one organ prior to treatment were not identified in the responder group, five of these patients were in the non-responder group. In the non-responder group, all patients discontinued treatment due to deterioration of general condition during first-line treatment. Thus, none of them were able to start the second-line treatment. CONCLUSION: The results of this study may suggest that early diagnosis and initiation of treatment before multiple organ metastasis development and PS decline may have clinical implications that could lead to improved treatment response in patients with LCNEC.

Early recurrence factors in patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND: The clinical characteristics and risk factors for cancer recurrence have not been well evaluated regarding early recurrence in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) who receive concurrent chemoradiotherapy (CRT). The aim of this study was to determine the clinical characteristics and risk factors of patients with stage III unresectable LA-NSCLC treated with CRT who developed early recurrence. METHODS: We retrospectively reviewed the clinical records of 46 patients diagnosed with stage III unresectable LA-NSCLC treated with CRT at our center between July 2012 and July 2021. A tumor proportion score (TPS) < 50% was defined as "low expression" and a TPS > 50% was defined as "high expression." RESULTS: A total of 17 (37.0%) patients had a confirmed recurrence within 1 year of treatment. More patients had a lower body mass index in the early recurrence group than in the later recurrence group (p = 0.038). A higher number of patients in the late recurrence group underwent surgery after CRT (p = 0.036). Patients with a higher TPS were more likely to experience late recurrence than early recurrence (p = 0.001), whereas more patients with stage N3 disease were in the early recurrence group (p = 0.011). Multivariate analysis identified lower TPS expression as an independent risk factor for early recurrence after CRT. Overall survival was prolonged in the late recurrence group (p < 0.001). CONCLUSIONS: A lower TPS may be a predictor of early recurrence after CRT in patients with LA-NSCLC. These patients should be closely monitored for post-treatment recurrence.

Efficacy and predictors of rechallenge with immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: The efficacy of rechallenge with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients has not yet been fully clarified. This study aimed to identify the clinical characteristics of patients with NSCLC who benefited from rechallenge with ICIs. METHODS: We retrospectively reviewed the clinical records of 24 patients who were diagnosed with NSCLC and rechallenged with ICIs between August 2016 and July 2021. RESULTS: Of the 24 patients included in the study, 11 were in the responder group (45.8%) and 13 in the nonresponder group (54.2%). The number of patients who used a different ICI from that used in the initial therapy was significantly higher in the responder group than in the nonresponder group (p = 0.006). Multivariate analysis identified lung metastasis and female sex as significant independent risk factors for nonresponse to rechallenge with ICIs. Compared to the nonresponder group, the duration of treatment after rechallenge with ICIs was significantly longer in the responder group (p = 0.016), and there was a trend toward longer overall survival (p = 0.059). CONCLUSIONS: Patients with lung cancer who were rechallenged with ICIs and without progressive disease after initial ICI therapy were able to continue ICI therapy for a longer period of time. This may be associated with longer survival. Patients with lung metastases and female patients are more likely to be nonresponsive to rechallenge with ICIs. Administration of a different type of ICI from that used in the initial ICI therapy may result in disease control.

Risk factors for acute exacerbation in lung cancer complicated by interstitial lung disease with slight reticular shadows.

BACKGROUND: The risk of cancer treatment-related acute exacerbation (AE) in patients with lung cancer and mild interstitial lung disease (ILD) on imaging, classified as indeterminate for usual interstitial pneumonia (UIP), has not previously been clarified. METHODS: We retrospectively reviewed the clinical records of 27 patients with lung cancer and ILD who were diagnosed and treated from April 2016 to March 2021. RESULTS: Among the 27 patients, 21 were classified as indeterminate for UIP and six as UIP/probable UIP; furthermore, 10 (46.6%) and three (50%) patients from each group, respectively, developed treatment-related AEs. No significant difference was observed regarding the incidence of AEs between the two groups. However, significantly more patients in the AE group received immune checkpoint inhibitors (ICIs) compared to the non-AE group (p = 0.021). Multivariate analysis revealed that the use of ICIs was a significant independent risk factor for treatment-related AEs. CONCLUSIONS: Lung cancer patients with mild ILD suggestive of indeterminate for UIP and UIP patterns are at an increased risk for treatment-related AEs. Furthermore, ICI use is an independent risk factor for AEs in patients with lung cancer complicated by ILD, and ICIs should be used with great caution.

Second SVC stent treatment for tumour ingrowth.

We herein report a case of lung cancer with recurrent superior vena cava (SVC) syndrome, which was treated with additional stent placement. Our report suggests the possibility that additional SVC stent placement is an option for treatment of tumour ingrowth, even in patients with poor performance status.

Bipolar Mood Tendency and Frontal Activation Using a Multichannel Near Infrared Spectroscopy.

UNLABELLED: This study aims to examine the association of frontal functioning with subclinical bipolar spectrum by a newly developed convenient method. We investigated subclinical bipolar tendency and frontal lobe activation during word productions using multi-channel near infrared spectroscopy. PARTICIPANTS: 44 healthy university students (mean ages 20.5 years old, and 29 female) gave their written informed consent, and we strictly protected privacy and anonymity was carefully preserved. A 13-items self-report questionnaire (Mood Disorders Questionnaire; MDQ) and a 16-channel near-infrared spectroscopy were used to compare frontal activations between two samples divided by median (4 points) of the total MDQ scores and to analyze correlations between relative changes of cerebral blood volume and bipolarity levels. There was no case suspected as bipolar disorders by MDQ screening (mean 3.4, max 10). Significant differences in lower activations were noted in the right and left pre-frontal cortex (PFC) with higher bipolarity scores using the specific software to analyze the NIRS waveform (P<0.05). Total MDQ were correlated significantly with frontal activation negatively in many channels; therefore, we conducted multiple linear regression to select significant frontal activations using the MDQ as a dependent variable. Stepwise method revealed that activation in left lateral PFC was negatively associated to bipolar tendency, and this regression model was significant (R2=0.10, F=4.5, P=0.04). Differences in frontal functioning suggest that subclinical bipolar tendencies might be related to left lateral PFC activations. It should be confirmed whether the identical pattern can be identified for clinical subjects with bipolar disorders.

Follow-up study of female delinquent adolescents in a detention centre: effectiveness of psychiatric intervention as a mental health service.

RESULTS: of previous studies suggest that many female offenders have co-morbid psychiatric disorders, which require mental health services. However, few longitudinal studies examined subjects during incarceration or detention. This study compares depressive symptoms, abnormal eating behaviour and impulsivity before release from a detention centre and after incarceration, thereby indicating the effectiveness of psychiatric intervention in a Japanese detention centre. METHOD: Of 64 young women, 36 were followed up. Self-report measures were used to assess depression, eating behaviour and impulsivity after incarceration and one month before release. RESULT: s: Of the 36 participants, nine were diagnosed using the MINI-kids as needing mental health services. Those who received psychiatric intervention were diagnosed as having major depression and/or post-traumatic stress disorder. Significant main effects of intervention and effects of time were shown in the DSD. The EAT-26 score demonstrated the significance of the effects of time and interaction. In the BIS-11 scores, neither intervention nor time showed significant effects. CONCLUSIONS: Results of this study showed that the time course and psychiatric intervention contributed to recovery of depression and therapeutic intervention. The time course might reduce eating problems. Psychiatric intervention might be necessary for female juvenile detainees, which presents an important issue for future studies.

Trauma exposure and posttraumatic stress disorder in delinquent female adolescents.

BACKGROUND: Although juveniles within the justice system have high psychiatric morbidity, few comprehensive investigations have shown posttraumatic stress disorder (PTSD) in female delinquents. Here, we aim to describe the nature and extent of PTSD and trauma exposure and to clarify the relationships among comorbidity and psychosocial factors in juvenile female offenders. METHOD: Sixty-four girls were randomly interviewed using structured tools. Self-report measures were used to assess depression, eating behaviour, impulsivity and parental attitude. RESULTS: The PTSD prevalence was 33%, and 77% of the female juvenile offenders had been exposed to trauma. The offenders with PTSD showed a significantly high psychiatric comorbidity. Depression and adverse parenting were associated with PTSD development, and abnormal eating was also correlated with PTSD symptoms. Marked differences in the frequency and intensity of PTSD evaluation depending on the type of comorbidity and trauma were observed. CONCLUSIONS: Incarcerated young females in Japan have serious trauma-related problems, and the degree of depression is a strong predictor of PTSD development and symptoms. This study highlights the importance of adequate diagnosis and treatment of PTSD in delinquent female adolescents.