Protocol for the nationwide registry of patients with polycystic kidney disease: japanese national registry of PKD (JRP).

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are major genetic polycystic kidney diseases that can progress to end-stage kidney disease (ESKD). Longitudinal data on the clinical characteristics associated with clinical outcomes in polycystic kidney disease (PKD), including the development of ESKD and cardiovascular disease (CVD) are lacking in Japan. To address this unmet need the authors are establishing a novel, web-based, Nationwide Cohort Registry Study-the Japanese Registry of PKD (JRP). METHODS: The JRP is a prospective cohort study for ADPKD (aim to recruit n = 1000 patients), and both a retrospective and prospective study for ARPKD (aim to recruit n = 100). In the prospective registry, patients will be followed-up for 10 years every 6 months and 12 months for patients with ADPKD and ARPKD, respectively. Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on April 1, 2024, with recruitment ending on March 31, 2029. (jRCT 1030230618). RESULTS: Data to be collected include: baseline data, demographics, diagnostic and genetic information, radiological and laboratory findings, and therapeutic interventions. During follow-up, clinical events such as development of ESKD, hospitalization, occurrence of extra kidney complications including CVD events, and death will be recorded, as well as patient-reported health-related quality of life for patients with ADPKD. CONCLUSIONS: The JRP is the first nationwide registry study for patients with ADPKD and ARPKD in Japan, providing researchers with opportunities to advance knowledge and treatments for ADPKD and ARPKD, and to inform disease management and future clinical practice.

Tracheobronchial Adenoid Cystic Carcinoma Treated Successfully With Chemoradiotherapy Followed by Durvalumab: A Case Report.

BACKGROUND/AIM: Tracheobronchial adenoid cystic carcinoma (ACC) is a rare type of malignancy. Although complete resection is standard treatment for localized ACC, treatment for unresectable ACC has not been established. It is unclear whether concurrent chemoradiotherapy (CCRT) followed by immune checkpoint inhibitor (ICI) therapy is effective for ACC. CASE REPORT: A 49-year-old man was admitted to our hospital for the treatment of dyspnea and thickening of the bronchial wall from the tracheal carina to the left main bronchus, as observed on a CT scan. Systemic examinations and transbronchial biopsy led to a diagnosis of locally advanced ACC. Although radiotherapy and chemotherapy are not regarded as very sensitive for ACC, a favorable response was obtained with CCRT. Following CCRT, he received ICI therapy with durvalumab for 1 year. The patient has remained in a stable condition 18 months after therapy, with no recurrence. CONCLUSION: ICI after CCRT might be a promising treatment option for unresectable tracheobronchial ACC.

Gene Polymorphisms of NLRP3 Associated With Plasma Levels of 4ß-Hydroxycholesterol, an Endogenous Marker of CYP3A Activity, in Patients With Asthma.

Inflammation decreases the activity of cytochrome P450 3A (CYP3A). Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is responsible for regulating the inflammatory response, and its genetic polymorphisms have been linked to inflammatory diseases such as asthma. However, there have been few studies on the effect of NLRP3 on CYP3A activity. We aimed to investigate the association between polymorphisms in the NLRP3 gene and plasma 4ß-hydroxycholesterol (4ßOHC), an endogenous marker of CYP3A activity, in patients with asthma. In this observational study including 152 adult asthma patients, we analyzed 10 NLRP3 gene single-nucleotide polymorphisms (SNPs). Plasma 4ßOHC levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that five SNPs were associated with significantly lower plasma 4ßOHC concentrations. Among these SNPs, rs3806265, rs4612666, rs1539019, and rs10733112 contributed to a significant increase in plasma IL-6 concentrations. Moreover, a multivariate regression model showed that the rs3806265 TT, rs4612666 CC, rs1539019 AA, and rs10733112 TT genotypes were significant factors for decreased plasma 4ßOHC, even after including patient background factors and CYP3A5*3 (rs776746) gene polymorphisms as covariates. These results were also observed when plasma 4ßOHC concentrations were corrected for cholesterol levels. We conclude that NLRP3 gene polymorphisms are involved in increasing plasma IL-6 concentrations and decreasing plasma 4ßOHC concentrations in patients with asthma. Therefore, NLRP3 gene polymorphisms may be a predictive marker of CYP3A activity in inflammatory diseases such as asthma.

Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 202 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg. CONCLUSIONS: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.

Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy.

Tolvaptan, an oral vasopressin V2 receptor antagonist, reduces renal volume expansion and loss of renal function in patients with autosomal dominant polycystic kidney disease (ADPKD). Data for predictive factors indicating patients more likely to benefit from long-term tolvaptan are lacking. Data were retrospectively collected from 55 patients on tolvaptan for 6 years. Changes in renal function, progression of renal dysfunction (estimated glomerular filtration rate [eGFR], 1-year change in eGFR [ΔeGFR/year]), and renal volume (total kidney volume [TKV], percentage 1-year change in TKV [ΔTKV%/year]) were evaluated at 3-years pre-tolvaptan, at baseline, and at 6 years. In 76.4% of patients, ΔeGFR/year improved at 6 years. The average 6-year ΔeGFR/year (range) minus baseline ΔeGFR/year: 3.024 (-8.77-20.58 mL/min/1.73 m2). The increase in TKV was reduced for the first 3 years. A higher BMI was associated with less of an improvement in ΔeGFR (p = 0.027), and family history was associated with more of an improvement in ΔeGFR (p = 0.044). Hypernatremia was generally mild; 3 patients had moderate-to-severe hyponatremia due to prolonged, excessive water intake in response to water diuresis-a side effect of tolvaptan. Family history of ADPKD and baseline BMI were contributing factors for ΔeGFR/year improvement on tolvaptan. Hyponatremia should be monitored with long-term tolvaptan administration.

Disease progression and changes in KL-6 in patients with limited cutaneous systemic sclerosis-associated interstitial lung disease.

BACKGROUND: Little is known about the annual change in Krebs von Lungen-6 (KL-6) and its correlation with forced vital capacity (FVC) in limited cutaneous systemic sclerosis-associated interstitial lung disease (lcSSc-ILD). We aimed to clarify the correlation during the clinical course. METHODS: We retrospectively reviewed data from consecutive patients with lcSSc-ILD. We measured FVC and KL-6 annually and calculated their annual changes using the difference in absolute values. Decline in FVC was defined as annual decline in FVC ≥5 %. RESULTS: Thirty-eight patients with SSc-ILD were included. The median age was 62 years and 58 % were female. The median FVC was 87.3 % and the median KL-6 was 1629 U/ml. The median observation period was 55.2 months and the annual changes in FVC and KL-6 were evaluated 151 times simultaneously. The annual change in KL-6 had a significant negative correlation with that in FVC in the first year from the initial evaluation (from the baseline to one-year follow-up) (r = -0.819, p < 0.01), but not after the first year. In the multivariable analysis adjusted by age, sex, and FVC at each year, the annual change of KL-6 (per 100 U/ml) was significantly associated with decline in FVC in the first year (odds ratio: 3.03, 95 % confidence interval: 1.21-7.59, p = 0.02), but not after the first year. CONCLUSIONS: Only in the first year from the initial evaluation, there was negative correlation between the annual change in FVC and that in KL-6 and the annual elevation in KL-6 was associated with decline in FVC in patients with lcSSc-ILD.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Physical activity in idiopathic pulmonary fibrosis: Longitudinal change and minimal clinically important difference.

BACKGROUND AND OBJECTIVE: Reference values of physical activity to interpret longitudinal changes are not available in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to define the minimal clinical important difference (MCID) of longitudinal changes in physical activity in patients with IPF. METHODS: Using accelerometry, physical activity (steps per day) was measured and compared at baseline and 6-months follow-up in patients with IPF. We calculated MCID of daily step count using multiple anchor-based and distribution-based methods. Forced vital capacity and 6-minute walk distance were applied as anchors in anchor-based methods. Effect size and standard error of measurement were used to calculate MCID in distribution-based methods. RESULTS: One-hundred and five patients were enrolled in the study (mean age: 68.5 ± 7.5 years). Step count significantly decreased from baseline to 6-months follow-up (-461 ± 2402, p = .031). MCID calculated by anchor-based and distribution-based methods ranged from 570-1358 steps. CONCLUSION: Daily step count significantly declined over 6-months in patients with IPF. MCID calculated by multiple anchor-based and distribution-based methods was 570 to 1358 steps/day. These findings contribute to interpretation of the longitudinal changes of physical activity that will assist its use as a clinical and research outcome in patients with IPF.

Real-World Results of Stereotactic Body Radiotherapy for 399 Medically Operable Patients with Stage I Histology-Proven Non-Small Cell Lung Cancer.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

Internal Trapping of a Growing Ruptured Dissecting Aneurysm of the A1 Segment: A Case Report and Literature Review.

A 47-year-old man presented with sudden-onset headache and Fisher group 3 subarachnoid hemorrhage. The World Federation of Neurological Surgeons grade was II. Digital subtraction angiography (DSA) only showed a vessel wall irregularity in the A1 segment of the right anterior cerebral artery (ACA), but an obvious bleeding source was not detected. Repeat angiography showed a tiny aneurysmal dilatation in the A1 segment with an intimal flap. The aneurysm enlarged on subsequent angiograms. Dissecting aneurysm was diagnosed, and the patient underwent internal trapping of the A1 segment to prevent rerupture. Postoperative DSA showed complete obliteration of the dissected segment. Magnetic resonance imaging showed a clinically silent cerebral infarction in the territory of the A1 segment perforators. Parent vessel occlusion for a dissected A1 segment can be effective, provided that sufficient collateral blood flow from the contralateral ACA is observed. We recommend endovascular trapping in this setting and hope that fellow clinicians select this approach for this rare pathology.

PKD1 Mutation Is a Biomarker for Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 500-4000 people worldwide. Genetic mutation is a biomarker for predicting renal dysfunction in patients with ADPKD. In this study, we performed a genetic analysis of Japanese patients with ADPKD to investigate the prognostic utility of genetic mutations in predicting renal function outcomes. METHODS: Patients clinically diagnosed with ADPKD underwent a panel genetic test for germline mutations in PKD1 and PKD2. This study was conducted with the approval of the Ethics Committee of Juntendo University (no. 2019107). RESULTS: Of 436 patients, 366 (83.9%) had genetic mutations. Notably, patients with PKD1 mutation had a significantly decreased ΔeGFR/year compared to patients with PKD2 mutation, indicating a progression of renal dysfunction (-3.50 vs. -2.04 mL/min/1.73 m2/year, p = 0.066). Furthermore, PKD1 truncated mutations had a significantly decreased ΔeGFR/year compared to PKD1 non-truncated mutations in the population aged over 65 years (-6.56 vs. -2.16 mL/min/1.73 m2/year, p = 0.049). Multivariate analysis showed that PKD1 mutation was a more significant risk factor than PKD2 mutation (odds ratio, 1.81; 95% confidence interval, 1.11-3.16; p = 0.020). CONCLUSIONS: The analysis of germline mutations can predict renal prognosis in Japanese patients with ADPKD, and PKD1 mutation is a biomarker of ADPKD.

Changes in patient-reported outcomes in patients with non-idiopathic pulmonary fibrosis fibrotic interstitial lung disease and progressive pulmonary fibrosis.

Background: Health-related quality of life (HRQoL) captures different aspects of the fibrotic interstitial lung disease (FILD) evaluation from the patient's perspective. However, little is known about how HRQoL changes in patients with non-idiopathic pulmonary fibrosis (IPF) FILD, especially in those with progressive pulmonary fibrosis (PPF). The aim of this study is to clarify whether HRQoL deteriorates in patients with non-IPF FILD and to evaluate the differences in the changes in HRQoL between those with and without PPF. Methods: We collected data from consecutive patients with non-IPF FILD and compared annual changes in HRQoL over 2 years between patients with PPF and those without. The St George's respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were used to assess HRQoL. Changes in the SGRQ and CAT scores for 24 months from baseline were evaluated with a mixed-effect model for repeated measures. Results: A total of 396 patients with non-IPF FILD were reviewed. The median age was 65 years and 202 were male (51.0%). The median SGRQ and CAT scores were 29.6 and 11, respectively. Eighty-six (21.7%) showed PPF. Both SGRQ and CAT scores were significantly deteriorated in patients with PPF compared to those without PPF (p < 0.01 for both). Clinically important deterioration in the SGRQ and CAT scores were observed in 40.0 and 35.7% of patients with PPF and 11.7 and 16.7% of those without, respectively. PPF was significantly associated with clinically important deterioration in the SGRQ score (odds ratio 5.04; 95%CI, 2.61-9.76, p < 0.01) and CAT score (odds ratio 2.78; 95%CI, 1.27-6.06, p = 0.02). Conclusion: The SGRQ and CAT scores were significantly deteriorated in patients with non-IPF FILD and PPF. Considering an evaluation of HRQoL would be needed when assessing PPF.

Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer.

BACKGROUND: The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. METHODS: We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. RESULTS: Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). CONCLUSIONS: Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

Robot-Assisted Radical Cystectomy with Modified Vesica Ileale Padovana (VIP) Neobladder Configuration Using a Hybrid Approach: Initial Experience.

PURPOSE: We developed a new technique to fold a neobladder (NB) simply by using a modified Vesica Ileale Padovana (VIP) with a hybrid approach. We provide a step-by-step description of our technique as it was used in this initial experience. METHODS: A total of 10 male patients with a median age of 66 years underwent robot-assisted radical cystectomy (RARC) with an orthotopic NB via a hybrid approach from March 2022 to February 2023. After the isolation of the bladder and bilateral pelvic lymphadenectomy, Wallace plate creation was performed, and the robot was undocked. We extracorporeally performed the removal of the specimen and a side-to-side ileoileal anastomosis, and then the VIP NB posterior plate was rotated 90 degrees counterclockwise using a 45 cm detubularized ileum. The robot was redocked; then, circumferential urethra-ileal anastomosis, side-to-middle anterior wall closure, and ureteric afferent limb anastomosis were performed. RESULTS: The median estimated blood loss was 524 mL, and the mean operative time was 496 min. Patients had a high continence rate, and no high-grade complications were observed. CONCLUSION: The NB configuration using the modified VIP method for a hybrid approach is a feasible surgical technique to minimize the movement of robotic forceps. In particular, it may be more useful in Asian individuals with narrow pelvises.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

AIM: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. METHODS: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. RESULTS: Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50-89 years), and the median tumor size was 23 mm (range: 6-50 mm). The median radiation dose was 40 Gy (range: 35-60 Gy) in five fractions (range: 4-8). The median follow-up period was 45 months (range: 0-103 months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. CONCLUSION: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

Interstitial pneumonia with autoimmune features and histologic usual interstitial pneumonia treated with anti-fibrotic versus immunosuppressive therapy.

BACKGROUND: Therapeutic strategies in patients with interstitial pneumonia with autoimmune features (IPAF) and histological usual interstitial pneumonia (UIP) pattern (IPAF-UIP) have not been thoroughly evaluated. We compared the therapeutic efficacy of anti-fibrotic therapy with that of immunosuppressive treatment for patients with IPAF-UIP. METHODS: In this retrospective case series, we identified consecutive IPAF-UIP patients treated with anti-fibrotic therapy or immunosuppressive therapy. Clinical characteristics, one-year treatment response, acute exacerbation, and survival were studied. We performed a stratified analysis by the pathological presence or absence of inflammatory cell infiltration. RESULTS: Twenty-seven patients with anti-fibrotic therapy and 29 with immunosuppressive treatment were included. There was a significant difference in one-year forced vital capacity (FVC) change between patients with anti-fibrotic treatment (4 in 27 improved, 12 stable, and 11 worsened) and those with immunosuppressive treatment (16 in 29 improved, eight stable, and five worsened) (p = 0.006). There was also a significant difference in one-year St George's Respiratory Questionnaire (SGRQ) change between patients with anti-fibrotic therapy (2 in 27 improved, ten stable, and 15 worsened) and those with immunosuppressive treatment (14 in 29 improved, 12 stable, and worsened) (p < 0.001). There was no significant difference in survival between the groups (p = 0.32). However, in the subgroup with histological inflammatory cell infiltration, survival was significantly better with immunosuppressive therapy (p = 0.02). CONCLUSION: In IPAF-UIP, immunosuppressive therapy seemed to be superior to anti-fibrotic treatment in terms of therapeutic response, and provided better outcomes in the histological inflammatory subgroup. Further prospective studies are needed to clarify the therapeutic strategy in IPAF-UIP.

Real-World Experience of the Comparative Effectiveness and Safety of Molnupiravir and Nirmatrelvir/Ritonavir in High-Risk Patients with COVID-19 in a Community Setting.

Molnupiravir (MOV) and nirmatrelvir/ritonavir (NMV/r) are efficacious oral antiviral agents for patients with the 2019 coronavirus (COVID-19). However, little is known about their effectiveness in older adults and those at high risk of disease progression. This retrospective single-center observational study assessed and compared the outcomes of COVID-19 treated with MOV and NMV/r in a real-world community setting. We included patients with confirmed COVID-19 combined with one or more risk factors for disease progression from June to October 2022. Of 283 patients, 79.9% received MOV and 20.1% NMV/r. The mean patient age was 71.7 years, 56.5% were men, and 71.7% had received ≥3 doses of vaccine. COVID-19-related hospitalization (2.8% and 3.5%, respectively; p = 0.978) or death (0.4% and 3.5%, respectively; p = 0.104) did not differ significantly between the MOV and NMV/r groups. The incidence of adverse events was 2.7% and 5.3%, and the incidence of treatment discontinuation was 2.7% and 5.3% in the MOV and NMV/r groups, respectively. The real-world effectiveness of MOV and NMV/r was similar among older adults and those at high risk of disease progression. The incidence of hospitalization or death was low.

Effectiveness of Repeated Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma-Consideration of the Locations of Target Lesions.

The present study retrospectively evaluated the efficacy of stereotactic body radiation therapy (SBRT), including repeated SBRT, for hepatocellular carcinoma. Participants comprised 220 HCC patients treated with SBRT in Hiroshima University Hospital between December 2008 and December 2021. Median overall survival (OS) and disease-free survival were 52 months (range, 45-64 months) and 17 months (range, 14-23 months), respectively. The 5-year local tumor recurrence rate was 3.4% (95% confidence interval (CI), 1.3-6.9%). Fifty-three patients underwent repeated SBRT (twice, 53 cases; three times, 10 cases; four times, 4 cases; five times, 1 case). Median interval between first and second SBRT was 20 months. Median OS from first SBRT was 76 months (95% CI, 50-102 months). Among patients with repeated SBRT, only one case showed local recurrence after second SBRT. Albumin-bilirubin score increased significantly from 6 to 12 months after repeated SBRT, both in the same segment and in remote segments, but the increase was not significant in the same segment. Only one case of grade 3 bile duct stricture was observed in patients who were treated with repeated SBRT. In conclusion, repeated SBRT provides good local control and a low risk of side effects.