Prospective therapeutic studies of disseminated extranodal large B-cell lymphoma including intravascular large B-cell lymphoma.

This study aimed to establish a standard treatment for disseminated extranodal large B-cell lymphoma, including intravascular large B-cell lymphoma (DEN-LBCL/IVL), and to validate the clinical diagnostic criteria we proposed. Between 2006 and 2016, 22 patients were enrolled in a clinical trial conducted by the Hokuriku Hematology Oncology Study Group. The first cycle of chemotherapy consisted of dose-reduced cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with delayed administration of rituximab. From the second to the sixth cycle, patients received conventional rituximab and CHOP therapy. The primary endpoint was overall survival (OS), while the secondary endpoints included the complete response (CR) rate and time to treatment failure (TTF). The results showed a CR rate of 73%, a median OS of 65 months, and a median TTF of 45 months. These findings indicate that patients with DEN-LBCL/IVL were effectively treated with our new chemoimmunotherapy regimen. Our clinical diagnostic criteria are useful for identifying patients who require early intervention.

IgG4-related Disease Concomitant with Diffuse Large B-cell Lymphoma.

A 77-year-old man presented with right inguinal lymphadenopathy and swollen parotid and submandibular glands bilaterally. Histopathology revealed germinal center B-cell type diffuse large B-cell lymphoma (DLBCL) in the inguinal lymph node. Lymphocyte and plasma cell infiltration in the submandibular gland with elevated serum IgG4 levels (13 g/L) prompted a diagnosis of IgG4-related disease (IgG4-RD). Systemic chemotherapy for DLBCL led to shrinkage of the lymph nodes and disappearance of the submandibular gland swelling, as confirmed by fluorodeoxyglucose-positron emission tomography/computed tomography. Although concomitant IgG4-RD and lymphoma have been reported, their simultaneous diagnosis is rare; therefore, a biopsy of all involved organs is crucial in cases with unusual organ involvement.

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.

Hyposecretion of cervical MUC5B is related to preterm birth in pregnant women after cervical excisional surgery.

PROBLEM: Excisional surgery for cervical intraepithelial neoplasia is a risk factor for preterm birth in subsequent pregnancies. However, the underlying mechanisms of this association remain unclear. We previously showed that cervical MUC5B, a mucin protein, may be a barrier to ascending pathogens during pregnancy. We thus hypothesized that hyposecretion of cervical MUC5B is associated with preterm birth after cervical excisional surgery. METHOD OF STUDY: This prospective nested case-control study (Study 1) included pregnant women who had previously undergone cervical excisional surgery across 11 hospitals. We used proteomics to compare cervicovaginal fluid at 18-22 weeks of gestation between the preterm and term birth groups. In another case-control analysis (Study 2), we compared MUC5B expression in nonpregnant uterine tissues between 15 women with a history of cervical excisional surgery and 26 women without a history of cervical surgery. RESULTS: The abundance of MUC5B in cervicovaginal fluid was significantly decreased in the preterm birth group (fold change = 0.41, p = .035). Among the 480 quantified proteins, MUC5B had the second highest positive correlation with gestational age at delivery in the combined preterm and term groups. The cervicovaginal microbiome composition was not significantly different between the two groups. Cervical length was not correlated with gestational age at delivery (r = 0.18, p = .079). Histologically, the MUC5B-positive area in the nonpregnant cervix was significantly decreased in women with a history of cervical excisional surgery (0.85-fold, p = .048). The distribution of MUC5B-positive areas in the cervical tissues of 26 women without a history of cervical excisional surgery differed across individuals. CONCLUSIONS: This study suggests that the primary mechanism by which cervical excisional surgery causes preterm birth is the hyposecretion of MUC5B due to loss of the cervical glands.

Fatty Degeneration of the Rotator Cuff Muscles Improves in Shoulders with Successful Arthroscopic Rotator Cuff Repair: A Prospective Study Using Quantitative T2 Mapping Techniques, with 2-Year Follow-up.

Background: There remain arguments regarding whether fatty degeneration of the rotator cuff muscles improves following rotator cuff repair. The purpose of this study was to prospectively investigate changes in fatty degeneration of the rotator cuff muscles, quantitatively measured on magnetic resonance imaging (MRI) with use of transverse relaxation time (T2) mapping techniques, and to assess the relationship between these changes and clinical outcomes. Methods: Patients were included if they were scheduled for arthroscopic rotator cuff repair using the suture-bridge technique between June 2014 and December 2015, underwent preoperative MRI including the T2 mapping sequence, and consented to participate in the study. Exclusion criteria consisted of trauma within 2 months before preoperative MRI, isolated subscapularis tears, patch augmentation, neuromuscular disease, and a follow-up duration of <2 years. MRI scans were acquired preoperatively and at 2 years postoperatively, and T2 values of the supraspinatus and infraspinatus muscles were measured, with smaller T2 values indicating less fat content. Shoulders were evaluated on the basis of active range of motion (ROM), Constant and University of California Los Angeles Shoulder Rating Scale scores, shoulder external rotation strength with the arm at the side, and rotator cuff integrity on postoperative MRI. Results: A total of 103 patients (103 shoulders) with a mean age of 65 ± 9 years (range, 42 to 83 years) were included, of whom 52 were male and 51 were female. There were 13 partial, 18 small, 35 medium, 33 large, and 4 massive tears. Concomitant subscapularis tears were observed in 35 shoulders. Overall, ROM, clinical scores, and external rotation strength significantly improved postoperatively. Retears were found in 27 shoulders (26%). External rotation strength significantly improved postoperatively only in shoulders without a retear. Among shoulders without a retear, the postoperative T2 values of the supraspinatus and infraspinatus were significantly smaller than the preoperative values (p < 0.001 for both); however, no improvement was seen in shoulders with a retear. Conclusions: Shoulders with successful repair demonstrated significantly smaller T2 values postoperatively as well as significantly improved external rotation strength. Fatty degeneration of the cuff muscles can be reversed, at least in part, and muscle strength improves in shoulders with successful repair. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Rotator Cuff Tears are Significantly More Frequent in Recurrent Shoulder Instability Patients With Initial Dislocation at Age 40 or Older.

PURPOSE: To investigate and compare the pathologies and clinical outcomes of patients with traumatic anterior shoulder instability who underwent arthroscopic stabilization at 40 years or older between shoulders with initial dislocation before age 40 years and at 40 years or after. METHODS: Shoulders that underwent arthroscopic stabilization for recurrent traumatic anterior shoulder instability at 40 years or older with a minimum of 2-year follow-up were included. The subjects were divided into 2 groups according to age at initial dislocation after propensity score matching to reduce potential bias: younger than 40 years (group 1) and 40 years or older (group 2). Radiographic findings, pathologies, clinical outcomes, and complications were compared between the groups. RESULTS: Group 1 included 56 shoulders in 56 patients (26 men and 30 women) with a mean age of 51 years (range, 40-77 years). Group 2 included 28 shoulders in 28 patients (13 men and 15 women) with a mean age of 51 years (range, 40-77 years). Glenoid bone loss was greater in group 1 than in group 2 (P = .004). Rotator cuff tears were more frequently observed in group 2 than in group 1 (P < .001). Both groups showed significant improvement in the West Ontario Shoulder Instability Index score (P < .001 for each) and flexion (P < .001 for each). The recurrence rate was 4% in group 1 and 7% in group 2. CONCLUSIONS: Rotator cuff tears are significantly more frequent in recurrent shoulder instability patients with initial dislocation at age 40 or older. Arthroscopic stabilization yielded a low recurrence rate and favorable outcomes with a good return-to-sport rate in patients 40 years or older. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

Desquamative Interstitial Pneumonia with Progressive Pulmonary Fibrosis.

A 70-year-old man who smoked was referred to our hospital because of progressive cough and dyspnea. Radiologic images showed ground-glass attenuation predominantly in the lower lung lobes. A surgical lung biopsy was performed, and a diagnosis of desquamative interstitial pneumonia (DIP) was made. The patient's symptoms improved with smoking cessation and steroid treatment, but the ground-glass attenuation did not completely resolve. At 10 years after the diagnosis, the fibrotic lesions deteriorated and treatment with nintedanib was subsequently initiated. Careful observation is needed in patients with DIP whose lung involvement does not completely improve with initial treatment.

Shear stress in the intervillous space promotes syncytial formation of iPS cells-derived trophoblasts†.

The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.

Relationship between duration of atrial fibrillation and right heart structure remodeling as assessed by 3-dimensional transesophageal echocardiography.

BACKGROUND: Tricuspid valve (TV) remodeling occurs in patients with atrial fibrillation (AF); however, the affecting factor related to TV remodeling in AF remains to be elucidated. We sought to explore whether the AF persistence itself affects right heart remodeling. METHODS: A total of 372 lone AF patients (234 paroxysmal AF [paroxAF] and 138 persistent AF [persAF]) who underwent 3-dimensional transesophageal echocardiography (3D-TEE) was retrospectively reviewed. The duration from first-detected episode of AF to the TEE exam date was defined as AF duration. RESULTS: PersAF patients had a larger TV area index (625.4 vs 719.0 mm2/m2; P < 0.001) and a higher right atrium area-to-right ventricle end-systolic area ratio (RA/RVESA ratio, 1.7 vs 1.9; P = 0.005) than paroxAF patients. The prevalence of AF-tricuspid regurgitation was higher in persAF than in paroxAF patients (1.3% vs 12.3%; P < 0.001). In persAF patients, AF duration was moderately correlated with TV diameter and 3D-TEE-derived TV annular area but not in paroxAF. On multivariable analysis, AF duration was independently associated with TV annular dilatation even after adjustment for RA/RVESA ratio and tricuspid regurgitation severity (ß 0.37 [95% CI: 0.77-1.81]; P < 0.001). Additionally, AF duration with cutoff values of 20 months for predicting TV annular dilatation and 37 months for predicting RA/RVESA ratio > 2.1 had both high diagnostic accuracies among persAF patients (both P < 0.01). CONCLUSIONS: AF duration itself is independently associated with right heart remodeling in persAF but not in paroxAF, such as TV annular dilatation and predominant RA remodeling which may lead to subsequent TR progression and adverse outcomes.

Left Atrial Stiffness Index as a Predictor of Effort Intolerance and Hemodynamics Evaluated by Invasive Exercise Stress Testing in Degenerative Mitral Regurgitation.

In patients with degenerative mitral regurgitation (DMR), peak oxygen consumption is the significant prognostic factor, and exercise intolerance has been considered a trigger for surgical intervention. The significant mitral regurgitation (MR) induces left atrial (LA) remodeling, but the significance of LA stiffness calculated by the ratio of E/e' to LA reservoir strain in degenerative MR has not been elucidated. A total of 30 patients with asymptomatic or minimally symptomatic grade ≥III + DMR underwent the cardiopulmonary exercising test simultaneously with invasive hemodynamic assessment. LA stiffness index significantly correlated with exercise hemodynamic deterioration, including pulmonary arterial wedge pressure (r = 0.71, p <0.01), systolic pulmonary arterial pressure at peak exercise (r = 0.73, p <0.01), and pulmonary circulatory reserve (mean pulmonary arterial pressure/cardiac output slope, r = 0.45, p = 0.012). Multiple linear regression analysis revealed that the higher LA stiffness index was significantly associated with decreased percent predicted peak oxygen consumption (per 0.1 increase, ß -4.0, 95% confidence interval -6.9 to -1.3, p <0.01) independently of MR deterioration during exercise. In conclusion, increased LA stiffness was associated with exercise intolerance through hemodynamic deterioration during exercise in patients with asymptomatic or minimally symptomatic severe DMR.

Characteristics of pregnancy complicated with type 1 and type 2 diabetes.

OBJECTIVE: Diabetes in pregnancy is a major risk factor for adverse perinatal outcomes such as congenital anomalies, hypertensive disorders of pregnancy (HDP), and macrosomia. For the mechanism of onset of type 1 and type 2 diabetes are different, we focused on the difference in perinatal outcomes between the type 1 and type 2 diabetes groups. MATERIALS AND METHODS: We retrospectively reviewed 22 pregnancies with type 1 diabetes and 15 pregnancies with type 2 diabetes, who were managed in our single center, with regard to maternal diabetes conditions during pregnancy and neonatal birthweight and blood glucose level. Furthermore, we checked the effect of continuous glucose monitoring and continuous subcutaneous insulin injection in pregnancies with type 1 diabetes. RESULTS: Type 1 diabetes in pregnancy was less controllable and increased neonatal birth weight and neonatal hypoglycemia within 2 h after birth after neonatal care unit admission. Continuous glucose monitoring and continuous subcutaneous insulin injection that are convenient to use, had a similar effect in the management of type 1 diabetes during pregnancy, compared with conventional diabetes treatment. In contrast, maternal BMI and HDP were increased in women with type 2 diabetes. CONCLUSION: In the management of pregnancy with diabetes, we should pay attention to the difference in pregnancy prognosis between type 1 and type 2 diabetes.

Laparoscopic resection for pedunculated focal nodular hyperplasia of the liver during pregnancy.

Focal nodular hyperplasia (FNH) is the second most common intrahepatic benign mass lesion; however, extremely rarely, FNH grows in an exophytic manner. It is unclear whether pedunculated FNH can be managed in the same way as intrahepatic FNH. A 35-year-old female presented with right upper quadrant pain, and dynamic enhanced computed tomography revealed an exophytic hyperdense mass lesion originating from the liver, suggesting a pedunculated FNH. Shortly thereafter, she conceived. Since there was a history of acute abdomen, as well as the possibility of torsion of the mass or sudden massive bleeding during pregnancy, laparoscopic resection was performed at 17 weeks of gestation. Her postoperative and pregnancy course was uneventful, and she delivered a baby by cesarean section at 41 weeks of gestation. Our case suggests that pedunculated FNH, unlike typical intrahepatic FNH, may be better managed by laparoscopic surgery during pregnancy, resulting in favorable maternal and fetal outcomes.

Partial pressure of carbon dioxide levels reflect disease severity in idiopathic pleuroparenchymal fibroelastosis.

BACKGROUND: Hypercapnia can cause a disturbance of consciousness and adversely affect a patient's general condition. Patients with interstitial lung disease seldom experience hypercapnia. Hypercapnia is a typical phenomenon in patients with pleuroparenchymal fibroelastosis (PPFE), especially in advanced stages. However, the clinical significance of hypercapnia in patients with idiopathic PPFE (iPPFE) has not been studied in detail. METHODS: We retrospectively selected patients with iPPFE who had undergone blood gas analysis. The first blood gas data obtained after iPPFE diagnosis were examined. The partial pressure of carbon dioxide (PCO2) levels and their association with characteristic iPPFE parameters, including the flat chest index (the ratio of the anteroposterior diameter of the thoracic cage to the transverse diameter of the thoracic cage), were investigated. RESULTS: A total of 47 patients with iPPFE were included in this study. The PCO2 level was moderately and inversely correlated with the forced vital capacity. (r = -0.431, P = 0.014), flat chest index (r = -0.497, P < 0.001), and body mass index (r = -0.313, P = 0.038) and was positively correlated with residual volume/total lung capacity. (r = 0.514, P < 0.01). A higher PCO2 level was also significantly associated with poorer prognosis in patients with iPPFE. CONCLUSIONS: PCO2 levels could be used as an indicator of disease severity in patients with iPPFE.

Obstetric pelvimetry by three-dimensional computed tomography in non-pregnant Japanese women: a retrospective single-center study.

OBJECTIVE: While a basic understanding of pelvic size and typology is still important for obstetricians, pelvic measurement data for Japanese women are very scarce. To our best knowledge, no large-scale pelvimetry studies of Japanese women have been made for the past 50 years. This study aimed to investigate the accurate size, particularly the obstetric conjugate (OC) and transverse diameter of the pelvic inlet (TD), of modern Japanese women, using three-dimensional (3D) computed tomography (CT), and to obtain their reference values. METHODS: This retrospective, single-center observational study enrolled Japanese non-pregnant women aged between 20 and 40 years, who underwent pelvic CT examination from 2016 to 2021. CT was performed for various reasons, including acute abdomen, search for cancer metastases, and follow-up of existing disease. However, no cases were taken for pelvic measurements. Pelvimetry was performed retrospectively using a 3D workstation. The OC was measured on a strict lateral view and the TD was measured on an axial-oblique view. Other clinical data, such as age, height, and weight, were also extracted from the medical charts and analyzed. RESULTS: A total of 1,263 patients were enrolled, with the mean age of 32.7 years (standard deviation [SD] 6.2). The mean height, weight, and body mass index were 158.8 cm (SD 5.8), 54.8 kg (SD 11.7), and 21.7 kg/m2 (SD 4.4), respectively. The mean OC length was 127.0 mm (SD 9.5, 95% confidence interval [CI] 126.5-127.5), while the mean TD length was 126.8 mm (SD 7.5, 95% CI 126.4-127.2). Both values were normally distributed. Height was significantly associated with OC (regression coefficient = 0.75 [95% CI 0.66-0.84], p < .001) and TD (regression coefficient = 0.63 [95% CI 0.56-0.70], p < .001). Age showed a weak but statistically significant positive association with TD (regression coefficient = 0.14 [95% CI 0.07-0.20], p < .001) and OC (regression coefficient = -0.10 [95% CI -0.18 to -0.01], p = .026). CONCLUSION: The 3D CT pelvimetry in 1,263 non-pregnant Japanese women of childbearing age revealed the mean OC and TD of 127.0 mm, and 126.8 mm, which were 11.8 mm and 4.3 mm larger, respectively, than those in the survey in 1972. Our data will be referred to in clinical practice as the standard pelvic measurement values for the Japanese population.

TAFRO Syndrome: A Disease Requiring Immediate Medical Attention.

TAFRO syndrome was first described in 2010, standing for thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly. Because the lymph node histopathology of TAFRO syndrome mimics idiopathic multicentric Castleman disease (iMCD), some researchers consider TAFRO syndrome to be a subtype of iMCD. However, the clinical features of TAFRO syndrome considerably differ from those of iMCD without TAFRO. The clinical features of patients with TAFRO syndrome with or without iMCD-histopathology are similar, and these patients require an accurate diagnosis and urgent treatment. Although a histological diagnosis, including a differential diagnosis, is important, lymph node involvement in patients with TAFRO syndrome is usually modest or sometimes absent. Furthermore, a bleeding tendency due to thrombocytopenia and severe anasarca hampers performing a biopsy. Nonetheless, patients with various other disorders may manifest TAFRO syndrome-like symptoms, making the differential diagnosis in borderline cases difficult. Therefore, the establishment of precise and specific biomarkers is important.

Cervical MUC5B and MUC5AC are Barriers to Ascending Pathogens During Pregnancy.

CONTEXT: Cervical excision is a risk factor for preterm birth. This suggests that the cervix plays an essential role in the maintenance of pregnancy. OBJECTIVE: We investigated the role of the cervix through proteomic analysis of cervicovaginal fluid (CVF) from pregnant women after trachelectomy surgery, the natural model of a lack of cervix. METHODS: The proteome compositions of CVF in pregnant women after trachelectomy were compared with those in control pregnant women by liquid chromatography-tandem mass spectrometry and label-free relative quantification. MUC5B/AC expression in the human and murine cervices was analyzed by immunohistochemistry. Regulation of MUC5B/AC expression by sex steroids was assessed in primary human cervical epithelial cells. In a pregnant mouse model of ascending infection, Escherichia coli or phosphate-buffered saline was inoculated into the vagina at 16.5 dpc, and the cervices were collected at 17.5 dpc. RESULTS: The expression of MUC5B/5AC in cervicovaginal fluid was decreased in pregnant women after trachelectomy concomitant with the anatomical loss of cervical glands. Post-trachelectomy women delivered at term when MUC5B/AC abundance was greater than the mean normalized abundance of the control. MUC5B levels in the cervix were increased during pregnancy in both humans and mice. MUC5B mRNA was increased by addition of estradiol in human cervical epithelial cells, whereas MUC5AC was not. In a pregnant mouse model of ascending infection, E. coli was trapped in the MUC5B/AC-expressing mucin of the cervix, and neutrophils were colocalized there. CONCLUSION: Endocervical MUC5B and MUC5AC may be barriers to ascending pathogens during pregnancy.

A case of welder's pneumoconiosis treated with corticosteroid followed by nintedanib.

A 32-year-old man who had worked as a welder for 13 years was hospitalized for a fever and hemosputum with dyspnea. He was diagnosed with welding fume-associated lung disease with alveolar hemorrhaging and acute respiratory failure. Despite surviving the acute phase with corticosteroid therapy, hypoxemia persisted after a month and a half, requiring home oxygen therapy. As a result of the introduction of nintedanib, his clinical findings gradually improved, and the patient was weaned from oxygen therapy after six months. Inhalation of a large amount of welding fumes in a short period can cause alveolar hemorrhaging and prolonged pulmonary dysfunction.