Objective Drug-induced interstitial lung disease (DI-ILD) is an adverse effect of the combination of gemcitabine and nab-paclitaxel (GnP) treatment that has raised concerns because the incidence rate of DI-ILD in the real world is higher than that reported in initial clinical trials. The present study assessed the cumulative incidence rate of DI-ILD among patients treated with GnP based on previously published studies and explored any potential bias in the results.

Methods We conducted a meta-analysis in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. The MEDLINE, Scopus, and Cochrane Library databases were searched from 2013 to 2024, using specific keywords. Randomized controlled trials, prospective studies, retrospective studies, and case-control studies that reported the incidence of interstitial lung disease (ILD) among patients treated with GnP were included. Two reviewers independently extracted the data from the included studies.

Results Nine studies involving 1,980 patients were included in this analysis. Nine studies were conducted in Japan. The pooled incidence of DI-ILD was 5.9%. A subgroup analysis revealed that smaller studies reported higher incidence rates (≤200 vs. ≥201 cases: 9.4% vs. 4.1%). There was significant heterogeneity and publication bias, suggesting that the variability in incidence rates was due to the study size and potential biases.

Conclusion The pooled incidence of ILD among patients treated with GnP was 5.9%. However, the results should be interpreted with caution because of the heterogeneity and publication bias. Further global studies are required to determine the true incidence of ILD.

Objective The controversy persists regarding whether the serum level of γ-glutamyltransferase (GGT), a marker of liver damage, is associated with hypertension irrespective of alcohol intake.

Methods We investigated the relationship between the GGT level and new-onset hypertension during a 10-year follow-up period in Japanese individuals who underwent annual health examinations (n=28,990). After excluding subjects without systolic blood pressure and GGT data and those with hypertension at baseline, a total of 18,618 subjects (men/women: 11,262/7,356, mean age: 44 years) were enrolled.

Results During the follow-up period, 2,753 men (24.4%) and 837 women (11.4%) developed hypertension. When the subjects were divided by quartiles of GGT at baseline (Q1-Q4), multivariable Cox proportional hazard model analyses after adjustment for age, sex, systolic blood pressure, body mass index, levels of uric acid, estimated glomerular filtration rate, family history of hypertension, habits of current smoking and alcohol drinking, and diagnosis of diabetes mellitus and dyslipidemia showed that hazard ratios (HRs) for the development of hypertension were significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group. A significant interaction was observed between alcohol drinking habits and the GGT level at baseline for the development of hypertension (p=0.022), and adjusted HRs were similarly significant in alcohol infrequent drinkers (≤5 days/week). However, the GGT level was not significantly associated with the development of hypertension in frequent alcohol drinkers (≥6 days/week).

Conclusion A high GGT level is an independent predictor of new-onset hypertension in infrequent alcohol drinkers but not in frequent drinkers.

Objective According to the current guidelines, the use of non-dihydropyridine calcium-channel blockers for the rate control of atrial fibrillation (AF) is contraindicated in patients with heart failure (HF), especially in those with a reduced ejection fraction (EF). However, there is little data supporting this recommendation. This study aimed to investigate the use of intravenous verapamil in patients with AF.

Methods We retrospectively studied 223 consecutive patients with AF treated with intravenous verapamil. We evaluated the clinical data of these patients, including any adverse events that occurred within 7 days.

Results The median age of the patients was 75.9 (67.8-80.7) years. Before administration, 71 patients (31.8%) had HF, 112 patients (62.6%) had a high B-type natriuretic peptide (BNP) level, and 28 patients (13.6%) had a left ventricular (LV) EF less than 50%. The mean administered dose of verapamil was 5.4±1.6 mg. The median heart rate (HR) was significantly reduced after verapamil administration [HR:145 (130-160) bpm to 95 (82-105) bpm, p<0.001]. Twenty-eight patients (12.6%) suffered from hypotension. Two patients had bradyarrhythmias. Within 7 days, cardiovascular death occurred in three patients (1.3%). A multivariate analysis revealed that pre sBP and hemoglobin, but not LVEF or BNP, were independently associated with adverse events.

Conclusion The intravenous administration of verapamil appears to be effective and safe for controlling the heart rate in most patients with AF, except in critically ill patients. However, further research is required to assess the safety of verapamil in patients for whom its use is not currently recommended by the clinical guidelines.

Objective Despite the recent development of various novel therapeutic approaches for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), optimal management of patients with R/R DLBCL who are elderly and/or unfit has not yet been established.

Methods We retrospectively analyzed the efficacy and safety of the R-mEPOCH regimen comprising rituximab, etoposide, vincristine, doxorubicin, carboplatin, and prednisolone in transplant-ineligible patients with R/R DLBCL.

Results In total, 22 patients were included in this study. The median patient age was 75 years old. The median number of prior lines of therapy was one (range, 1-5). The overall response rate was 68%, with 45% achieving complete response (CR) or unconfirmed CR and 23% achieving partial response. With a median follow-up of 27.8 months, the median progression-free survival and overall survival (OS) were 17.1 and 27.4 months, respectively. The 2- and 5-year OS rates were 50% and 28%, respectively. The most common grade ≥3 adverse events were neutropenia [n=18 (82%)], febrile neutropenia [n=16 (73%)], anemia [n=12 (55%)], and thrombocytopenia [n=8 (36%)]. The median total lifetime cumulative dose of anthracyclines was 281 mg/m² (range, 69-536 mg/m²) in doxorubicin equivalents. One case of grade 1 bradycardia occurred, leading to the discontinuation of R-mEPOCH. No other cardiac adverse events of grade ≥3 and/or discontinuation of treatment were observed.

Conclusion Our study suggests that the R-mEPOCH regimen may be an effective and tolerable salvage regimen for transplant-ineligible R/R DLBCL patients.

Objective White matter hyperintensity (WMH) is the most prominent magnetic resonance imaging (MRI) feature of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), clinically characterized by recurrent ischemic stroke. This study aimed to explore the association between WMH and symptomatic stroke in patients with CADASIL by quantifying the volume and features extracted from histogram-segmented WMH.

Methods Twenty-eight patients with CADASIL were retrospectively recruited. WMH was extracted from fluid-attenuated inversion recovery (FLAIR) images. A histogram analysis of WMH was performed using radiomics extension on a 3D slicer. We compared the histogram parameters between patients with and without symptomatic stroke.

Results Thirteen patients had no symptoms, while 15 had previous symptomatic stroke. Their characteristics were similar, except for a higher frequency of males among stroke patients (73.3 vs. 15.4%, respectively). Among the histogram features, the skewness of the FLAIR intensity histogram was significantly lower in patients with stroke than in those without stroke (-0.179 vs. 0.210, respectively, p=0.0287), but there was no significant difference regarding any other histogram features or the WMH volume. According to a multiple logistic regression analysis, sex and skewness remained significant (odds ratio: 40.870 and 0.0119, p=0.0136 and 0.0473, respectively).

Conclusion The skewness of the FLAIR WMH intensity histogram was significantly correlated with stroke in patients with CADASIL.

We herein report a case of hepatitis B virus (HBV) reactivation in a female patient in her 70s with isolated anti-hepatitis B core (IAHBc) antibodies [HB surface antigen (HBsAg)-negative, HB surface antibody (HBsAb)-negative, and HB core antibody (HBcAb)-positive], receiving rituximab-based chemotherapy for follicular lymphoma. Her serum HBV DNA was negative. The patient was treated with rituximab for 21 months, and 33 months after completion of treatment, her HBV DNA level increased to 5.1 Log IU/mL, and the patient developed hepatic failure. Tenofovir alafenamide fumarate treatment was initiated for HBV reactivation, and DNA was not detected 9 months later.

Relapsing polychondritis (RP) is a rare, progressive, immune-mediated systemic inflammatory disease of unknown etiology characterized by recurrent inflammation of cartilaginous structures. Approximately 30% of RP cases are associated with autoimmune disease. However, co-occurrence of RP and Crohn's disease (CD) has rarely been reported. We herein report a case of coexisting RP, CD, and pyoderma gangrenosum that was successfully treated with adalimumab in combination with methotrexate. We believe that this case and literature review will facilitate the accurate and prompt diagnosis and treatment of RP combined with CD and various other complications.

This report presents two cases of esophageal mucosal damage following peroral endoscopic myotomy (POEM) for esophageal motility disorders. In the first case, delayed perforation and mediastinitis occurred on postoperative day 15 and the patient was treated with endoscopic clipping and antibiotics. In the second case, although no perforation was observed, extensive mucosal injury developed the day after POEM which was successfully managed by fasting and antibiotic therapy. These findings highlight the need for careful patient management to minimize the risks associated with POEM, while maximizing its therapeutic benefits.

A 66-year-old male ex-smoker presented with fatigue and non-productive cough, as well as a 2-year history of ground-glass opacities. Deterioration on chest radiography and increased Krebs von den Lungen-6 levels coincided with the progression of diffuse ground-glass opacities on high-resolution computed tomography. Surgical lung biopsy revealed features consistent with desquamative interstitial pneumonia. Concurrent skin hardening and presence of anti-Scl-70 antibodies supported the diagnosis of systemic sclerosis. Treatment with oral corticosteroids proved to be effective, leading to radiographic improvement. The subsequent administration of cyclophosphamide and mycophenolate mofetil stabilized disease progression.

A 70-year-old male presented with infiltration, ground-glass opacities, and bronchiectasis on chest radiography, which indicated interstitial pneumonia. Clinical findings (thickening of the skin on the fingers, slight nail fold petechiae, and skin lesions resembling mechanic's hands) suggested early systemic sclerosis and/or polymyositis/dermatomyositis. However, anti-Scl-70, anti-centromere, and anti-aminoacyl tRNA synthetase (anti-ARS) antibodies were negative. Exertion-related oxygenation gradually worsened. Since the multiplex protein array confirmed anti-Zo and anti-Ro52/SSA1 antibody positivity, anti-ARS antibody syndrome was diagnosed and treated with steroids and immunosuppressive drugs. The patient was concurrently diagnosed with advanced colorectal cancer. Treating interstitial pneumonia first allowed for the subsequent treatment of colorectal cancer without worsening the condition.

Dipeptidyl peptidase-4 inhibitors (DPP-4is) are shown to be associated with the development of bullous pemphigoid (BP). Immune checkpoint inhibitors (ICIs) can lead to BP development. Therefore, the combination of DPP-4is and ICIs may predispose an individual to developing BP; however, few reports have focused on this issue. We herein report two patients with non-small-cell lung cancer complicated by diabetes mellitus (DM) who developed BP while receiving DPP-4is and ICIs. The clinical course of these patients suggests that the combination of DPP-4is and ICIs may carry a potential risk of BP development.

Dyskeratosis congenita (DC) is a rare genetic disorder that is caused by abnormal telomere shortening. We herein report the case of a 40-year-old man with classic DC characterized by a mucocutaneous triad complicated by pulmonary fibrosis and myelodysplastic syndrome (MDS). The telomere length of lymphocytes was extremely short (-3.3 standard deviations). We identified the germline mutation c.C91A in DKC1 gene. We also identified a somatic mutation c.C101T in the U2AF1 gene of leukocytes, which may be associated with MDS development. Nintedanib was started, but the patient died of bilateral pneumothorax 6 months after diagnosis.

Obinutuzumab-induced acute thrombocytopenia is characterized by a rapid decrease in the platelet count after administration. The underlying mechanisms remain unclear. However, we present novel laboratory findings related to its pathophysiology. A 65-year-old woman with follicular lymphoma developed acute thrombocytopenia within 24 hours after obinutuzumab administration. Laboratory results showed features resembling acute immune thrombocytopenic purpura, including an elevated immature platelet fraction, mildly increased thrombopoietin levels, elevated platelet-associated immunoglobulin G, and refractory to platelet transfusion. Our case and her laboratory findings suggest that increased platelet consumption might be involved in the development of obinutuzumab-induced acute thrombocytopenia.

We describe a case of immunological rejection occurring twice after cord blood transplantation (CBT) for mixed phenotype blast phase chronic myeloid leukemia that was successfully salvaged by haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PT-Cy). Pre-engraftment immune reaction (PIR) and subsequent hemophagocytic lymphohistiocytosis (HLH), likely due to HLA mismatch in the graft-versus-host (GVH) direction, lead to poor graft function (PGF) and graft failure (GF). This case highlights the pathophysiology of PIR, HLH, PGF, and GF, collectively termed "post-transplant cytokine syndrome." PT-Cy haplo-PBSCT, with wide donor availability and reduced infection risk leading to HLH via rapid engraftment, may be a suitable salvage option for post-CBT cytokine syndrome-related GF.

We herein present the case of a 73-year-old man with IgM multiple myeloma (IgM-MM) and t(11;14). The tumor cells showed a small lymphoplasmacytic morphology and dim expression of CD38 and CD138. The MYD 88^L265P mutation was found to be negative. After plasma exchange, bortezomib and dexamethasone treatments were refractory. Subsequent daratumumab, lenalidomide, and dexamethasone therapy failed to respond despite the standard therapy for non-IgM-MM. Subsequently, pomalidomide, cyclophosphamide, and dexamethasone therapies demonstrated a good response, and a stringent complete response was therefore achieved. This case highlights the need for different treatment strategies for IgM-MM compared with non-IgM-MM because the biological features of IgM-MM and non-IgM-MM are different.

A 17-year-old Japanese woman diagnosed with granulomatosis with polyangiitis (GPA) and was treated with immunotherapy suddenly developed an impaired consciousness, left hemiplegia, and conjugate eye deviation to the right. Magnetic resonance imaging showed an acute cerebral infarction in the right striatum and right middle cerebral artery (MCA) occlusion. As her GPA had worsened recently, intravenous methylprednisolone (IVMP) was started. Immediately after IVMP was started, recanalization of the MCA was detected on repeat cerebral angiography. Aspirin and argatroban dissolved the residual thrombi. A combination of IVMP and antithrombotic therapy may be effective for large-vessel occlusions associated with GPA.

41-year-old female became difficulty walking due to sensory ataxia in the limbs and trunk. A diagnosis of Sjögren's syndrome was made on the results of positive anti-SS-A antibody and a lip gland biopsy. Nerve conduction studies indicated sensory neuronopathy. The symptoms improved following treatment with plasma exchange, intravenous immunoglobulin, and intravenous methylprednisolone. Nine months later, the patient's sensory ataxia worsened. Nerve conduction studies revealed the coexistence of sensory neuronopathy and polyradiculoneuropathy. The symptoms improved following treatment with intravenous cyclophosphamide and intravenous immunoglobulin. This case represents the first instance of sensory neuronopathy and polyradiculoneuropathy coexisting as Sjögren's syndrome related neuropathy.

A 69-year-old man was admitted to our hospital because of progressive numbness in the lower legs and fingertips as well as a burning sensation in the soles of both feet. The patient was diagnosed with anti-myelin-associated glycoprotein (anti-MAG) neuropathy based on increased serum IgM levels and anti-MAG antibody titers. Atypical pulmonary mycobacteriosis was also suspected. Following treatment with tirabrutinib (a second-generation Bruton tyrosine kinase inhibitor), his symptoms improved and the anti-MAG antibody titer and IgM levels decreased. Tirabrutinib may therefore be an effective treatment option for anti-MAG neuropathy, particularly in patients at risk of infection.

Anifrolumab is a newly developed biological agent for patients with moderate-to-severe systemic lupus erythematosus (SLE). Anifrolumab neutralizes the signaling pathways mediated by type I interferons (IFNs), which are involved in viral clearance and anticancer immunity. Although susceptibility to viral infections has been reported in patients treated with anifrolumab, whether anifrolumab treatment increases the cancer risk in patients with SLE is unknown. We herin report a case of SLE that manifested as aggressive diffuse large B-cell lymphoma (DLBCL) after treatment with anifrolumab. The neutralization of type I IFNs by anifrolumab may promote the development of DLBCL owing to defective anticancer immunity.

An association between coronavirus disease 2019 (COVID-19) and concomitant varicella-zoster virus (VZV) reactivation has been proposed. We herein report a case of severe VZV pneumonia in a 73-year-old man who underwent corticosteroid tapering after recovering from COVID-19 and presented with fever, vesicular rashes, and hypoxemia. Chest computed tomography revealed ground-glass opacities (GGOs) and multiple granular shadows. Varicella-zoster virus was detected in the skin and bronchoalveolar lavage fluid. The patient was diagnosed with disseminated VZV reactivation and thereafter successfully recovered with acyclovir treatment. Physicians should consider the possibility of VZV reactivation when GGOs or patchy nodular shadows appear during the course of patients with COVID-19.

Pseudomonas aeruginosa (P. aeruginosa) infection, often diagnosed in immunocompromised patients, is a chronic disease. However, peritonsillar and deep cervical abscesses caused by P. aeruginosa are rare. We herein present the rare case of a 70-year-old male patient with a 5-day history of sore throat and difficult oral intake. The oral cavity was filled with pus and the left palatine tonsil was destroyed. A peritonsillar abscess caused by P. aeruginosa was diagnosed using a pus culture. Emergency incisions were made for tonsil drainage, tracheostomy, and antibacterial drug treatment. Despite infection resolution in 20 days, recovery from swallowing dysfunction required one year of rehabilitation.

A 60-year-old man with a history of radiation therapy 28 years ago for a benign disease (an aneurysmal bone cyst) was admitted with dyspnea and dysphagia. Computed tomography showed an 8-cm tumor invading the trachea and esophagus. His condition declined rapidly, and he died on day 27 of hospitalization. Autopsy revealed radiation-induced osteosarcoma. Radiation-induced sarcoma can develop even after radiotherapy for benign diseases, in which case the latency period might be longer. Furthermore, the prognosis depends on the location of the resectable tumor. Therefore, longer-term internal imaging follow-up should be performed after radiotherapy for benign diseases to detect early-stage sarcoma.

Hughes-Stovin syndrome (HSS) is an exceedingly rare disease characterized by thrombotic phlebitis and pulmonary or bronchial artery aneurysms. A 68-year-old man presented with ischemic colitis, and angiography revealed occlusion of the inferior mesenteric vein and arteriovenous malformation in the inferior mesenteric artery region. Medical treatment was unsuccessful, and a left hemicolectomy was therefore performed following coil embolization. Subsequently, a pulmonary artery aneurysm was incidentally detected, and coil embolization was performed. However, the patient developed deep vein thrombosis and a pulmonary embolism, which led to a diagnosis of HSS. To our knowledge, this is the first report of ischemic colitis as a presenting feature of HSS.