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Introduction: Follicular lymphoma is an indolent B-cell lymphoma that can involve the gastrointestinal tract, most commonly the small intestine. Although rituximab-based therapy is effective, transformation to diffuse large B-cell lymphoma (DLBCL) can occur and becomes difficult to diagnose after CD20 loss. Case Presentation: We report the case of a 64-year-old woman initially diagnosed with primary small intestinal follicular lymphoma who subsequently developed transformation to DLBCL 2 years after rituximab therapy. Double-balloon enteroscopy revealed progression of mucosal lesions, raising suspicion of histologic transformation. However, endoscopic biopsy was inconclusive because of the loss of CD20 expression, likely resulting from prior rituximab therapy. Surgical resection was performed to relieve intestinal obstruction and to establish a definitive diagnosis. Histopathological examination confirmed transformation to CD20-negative DLBCL. Conclusion: This case highlights the diagnostic limitation of endoscopic biopsy following rituximab therapy. Therefore, clinicians should be cautious in relying solely on endoscopic findings and remain open to surgical intervention to achieve a timely and accurate diagnosis.

Endoscopic submucosal dissection (ESD) of superficial gastric lesions located along the lesser curvature at the gastric angle is a challenging situation due to paradoxical movement and a protruding angle. The pocket-creation method (PCM) can overcome this difficulty by stabilizing the tip of the endoscope in the pocket and minimizing insufflation of the stomach, which enables horizontal and straight dissection. This study aims to clarify whether the PCM improves the technical outcomes of ESD of superficial gastric neoplasms along the lesser curvature at the angle. From October 2006 to June 2021, 158 gastric lesions along the lesser curvature at the angle were resected with needle-type knives. We retrospectively reviewed the records and divided them into the PCM group ( = 61) and the conventional method (CM) group ( = 97). The primary outcome measurement was dissection speed (in mm /min). The two groups were not significantly different for baseline characteristics such as macroscopic type and size except for the proportion of adenomas. The proportion of expert endoscopists was not significantly different between the two groups ( = 0.141). The dissection speed was significantly faster in the PCM group than in the CM group ( = 0.001). There were no holes in the resected specimens in the PCM group, while five lesions in the CM group (5%) had a hole ( = 0.182). There were no significant differences in the incidence of adverse events. This is the first study to show that the PCM outperforms the CM for ESD of lesions located along the lesser curvature at the gastric angle. The PCM facilitated ESD of these lesions by significantly increasing dissection speed when a needle-type knife is used with no increase in adverse events.

The resection strategy for rectal neuroendocrine tumors (NET) < 10 mm is not uniform. We compared the utility of underwater endoscopic mucosal resection (UEMR) to endoscopic submucosal resection with a ligation device (ESMR-L) to resect rectal NETs. Patients with rectal NET < 10 mm treated with UEMR or ESMR-L were included. Their medical records were retrospectively reviewed. Thirty-two patients were divided into a UEMR group ( = 7) and an ESMR-L group ( = 25). Histopathological diagnosis of NET by biopsy was known before resection in 43% (3/7) in the UEMR group and 68% (17/25) in the ESMR-L group, ( = 0.379). UEMR was performed on an outpatient basis for all patients, and 92% of ESMR-L (23/25) were performed as inpatient procedures ( < 0.001). The procedure time was significantly shorter in the UEMR group than in the ESMR-L group [median (IQR), min, 6 (5-8) vs. 12 (9-14), = 0.002]. resection and R0 resection rates were 100% in both groups. Pathological evaluations were predominantly NET G1 in both groups (UEMR: 7/7, 100% and ESMR-L: 23/25, 92%). Two patients in the ESMR-L group developed delayed bleeding, controlled by endoscopic hemostasis. Device costs were significantly higher in the ESMR-L group than the UEMR group by approximately US$180 [median (IQR), $90.45 (83.64-108.41) vs. $274.73 (265.86-292.45), < 0.001]. UEMR results in similar resection quality with shorter procedure time and lower costs compared to ESMR-L. We recommend UEMR for the resection of rectal NET < 10 mm.

BackgroundA phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority [OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79–1.06], and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported.MethodsThe intent-to-treat population enrolled in Japan was analyzed.ResultsOf 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (N = 81) or the SOR arm (N = 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR (HR 0.90; 95% CI 0.62–1.29). LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm.ConclusionsThe efficacy and safety of LEN in the Japanese population were similar to those in the overall population of REFLECT. With manageable adverse events, LEN is a new treatment option for Japanese patients with uHCC.Trial registration IDClinicalTrials.gov. No. NCT01761266.

In classical Hodgkin lymphoma (cHL)—characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells—tumor-associated macrophages (TAMs) play a pivotal role in tumor formation. However, the significance of direct contact between HRS cells and TAMs has not been elucidated. HRS cells and TAMs are known to express PD-L1, which leads to PD-1+ CD4+ T cell exhaustion in cHL. Here, we found that PD-L1/L2 expression was elevated in monocytes co-cultured with HRS cells within 1 h, but not in monocytes cultured with supernatants of HRS cells. Immunofluorescence analysis of PD-L1/L2 revealed that their upregulation resulted in membrane transfer called “trogocytosis” from HRS cells to monocytes. PD-L1/L2 upregulation was not observed in monocytes co-cultured with PD-L1/L2-deficient HRS cells, validating the hypothesis that there is a direct transfer of PD-L1/L2 from HRS cells to monocytes. In the patients, both ligands (PD-L1/L2) were upregulated in TAMs in contact with HRS cells, but not in TAMs distant from HRS cells, suggesting that trogocytosis occurs in cHL patients. Taken together, trogocytosis may be one of the mechanisms that induces rapid upregulation of PD-L1/L2 in monocytes to evade antitumor immunity through the suppression of T cells as mediated by MHC antigen presentation.

We aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA). From the database of a multicenter registry on OHCA patients, we included adult nontraumatic OHCA patients transported to the hospital with ongoing CPR. Based on the serum lactate levels during CPR, the patients were divided into four quartiles: Q1 (≤ 10.6 mEq/L), Q2 (10.6–14.1 mEq/L), Q3 (14.1–18.0 mEq/L), and Q4 (> 18.0 mEq/L). The primary outcome was 1-month survival. Among 5226 eligible patients, the Q1 group had the highest 1-month survival (5.6% [74/1311]), followed by Q2 (3.6% [47/1316]), Q3 (1.7% [22/1292]), and Q4 (1.0% [13/1307]) groups. In the multivariable logistic regression analysis, the adjusted odds ratio of Q4 compared with Q1 for 1-month survival was 0.24 (95% CI 0.13–0.46). 1-month survival decreased in a stepwise manner as the quartiles increased ( p for trend < 0.001). In subgroup analysis, there was an interaction between initial rhythm and survival ( p for interaction < 0.001); 1-month survival of patients with a non-shockable rhythm decreased when the lactate levels increased ( p for trend < 0.001), but not in patients with a shockable rhythm ( p for trend = 0.72). In conclusion, high serum lactate level during CPR was associated with poor 1-month survival in OHCA patients, especially in patients with non-shockable rhythm.

The ionosphere is one of the important sources for magnetospheric plasma, particularly for heavy ions with low charge states. We investigate the effect of solar illumination on the number flux of ion outflow using data obtained by the Fast Auroral SnapshoT (FAST) satellite at 3000–4150 km altitude from 7 January 1998 to 5 February 1999. We derive empirical formulas between energy inputs and outflowing ion number fluxes for various solar zenith angle ranges. We found that the outflowing ion number flux under sunlit conditions increases more steeply with increasing electron density in the loss cone or with increasing precipitating electron density (> 50 eV), compared to the ion flux under dark conditions. Under ionospheric dark conditions, weak electron precipitation can drive ion outflow with small averaged fluxes (~ 107 cm−2 s−1). The slopes of relations between the Poynting fluxes and outflowing ion number fluxes show no clear dependence on the solar zenith angle. Intense ion outflow events (> 108 cm−2 s−1) occur mostly under sunlit conditions (solar zenith angle < 90°). Thus, it is presumably difficult to drive intense ion outflows under dark conditions, because of a lack of the solar illumination (low ionospheric density and/or small scale height owing to low plasma temperature).

Patients who have acute myocardial infarction remain at major risk of cardiovascular events. We aimed to assess the effects of either human atrial natriuretic peptide or nicorandil on infarct size and cardiovascular outcome. We enrolled 1216 patients who had acute myocardial infarction and were undergoing reperfusion treatment in two prospective, single-blind trials at 65 hospitals in Japan. We randomly assigned 277 patients to receive intravenous atrial natriuretic peptide (0·025 μg/kg per min for 3 days) and 292 the same dose of placebo. 276 patients were assigned to receive intravenous nicorandil (0·067 mg/kg as a bolus, followed by 1·67 μg/kg per min as a 24-h continuous infusion), and 269 the same dose of placebo. Median follow-up was 2·7 (IQR 1·5–3·6) years for patients in the atrial natriuretic peptide trial and 2·5 (1·5–3·7) years for those in the nicorandil trial. Primary endpoints were infarct size (estimated from creatine kinase) and left ventricular ejection fraction (gauged by angiography of the left ventricle). 43 patients withdrew consent after randomisation, and 59 did not have acute myocardial infarction. We did not assess infarct size in 50 patients for whom we had fewer than six samples of blood. We did not have angiographs of left ventricles in 383 patients. Total creatine kinase was 66 459·9 IU/mL per h in patients given atrial natriuretic peptide, compared with 77 878·9 IU/mL per h in controls, with a ratio of 0·85 between these groups (95% CI 0·75–0·97, p=0·016), which indicated a reduction of 14·7% in infarct size (95% CI 3·0–24·9%). The left ventricular ejection fraction at 6–12 months increased in the atrial natriuretic peptide group (ratio 1·05, 95% CI 1·01–1·10, p=0·024). Total activity of creatine kinase did not differ between patients given nicorandil (70 520·5 IU/mL per h) and controls (70 852·7 IU/mL per h) (ratio 0·995, 95% CI 0·878–1·138, p=0·94). Intravenous nicorandil did not affect the size of the left ventricular ejection fraction, although oral administration of nicorandil during follow-up increased the left ventricular ejection fraction between the chronic and acute phases. 29 patients in the atrial natriuretic peptide group had severe hypotension, compared with one in the corresponding placebo group. Patients with acute myocardial infarction who were given atrial natriuretic peptide had lower infarct size, fewer reperfusion injuries, and better outcomes than controls. We believe that atrial natriuretic peptide could be a safe and effective adjunctive treatment in patients with acute myocardial infarction who receive percutaneous coronary intervention.

Cortical microinfarcts (CMIs) observed in brains of patients with Alzheimer’s disease tend to be located close to vessels afflicted with cerebral amyloid angiopathy (CAA). CMIs in Alzheimer’s disease are preferentially distributed in the arterial borderzone, an area most vulnerable to hypoperfusion. However, the causal association between CAA and CMIs remains to be elucidated. This study consists of two parts: (1) an observational study using postmortem human brains ( n  = 31) to determine the association between CAA and CMIs, and (2) an experimental study to determine whether hypoperfusion worsens CAA and induces CMIs in a CAA mouse model. In postmortem human brains, the density of CMIs was 0.113/cm 2 in mild, 0.584/cm 2 in moderate, and 4.370/cm 2 in severe CAA groups with a positive linear correlation ( r  = 0.6736, p  < 0.0001). Multivariate analysis revealed that, among seven variables (age, disease, senile plaques, neurofibrillary tangles, CAA, atherosclerosis and white matter damage), only the severity of CAA was a significant multivariate predictor of CMIs ( p  = 0.0022). Consistent with the data from human brains, CAA model mice following chronic cerebral hypoperfusion due to bilateral common carotid artery stenosis induced with 0.18-mm diameter microcoils showed accelerated deposition of leptomeningeal amyloid β (Aβ) with a subset of them developing microinfarcts. In contrast, the CAA mice without hypoperfusion exhibited very few leptomeningeal Aβ depositions and no microinfarcts by 32 weeks of age. Following 12 weeks of hypoperfusion, cerebral blood flow decreased by 26% in CAA mice and by 15% in wild-type mice, suggesting impaired microvascular function due to perivascular Aβ accumulation after hypoperfusion. Our results suggest that cerebral hypoperfusion accelerates CAA, and thus promotes CMIs.