Machine/deep learning-assisted hemoglobin level prediction using palpebral conjunctival images.

Palpebral conjunctival hue alteration is used in non-invasive screening for anaemia, whereas it is a qualitative measure. This study constructed machine/deep learning models for predicting haemoglobin values using 150 palpebral conjunctival images taken by a smartphone. The median haemoglobin value was 13.1 g/dL, including 10 patients with <11 g/dL. A segmentation model using U-net was successfully constructed. The segmented images were subjected to non-convolutional neural network (CNN)-based and CNN-based regression models for predicting haemoglobin values. The correlation coefficients between the actual and predicted haemoglobin values were 0.38 and 0.44 in the non-CNN-based and CNN-based models, respectively. The sensitivity and specificity for anaemia detection were 13% and 98% for the non-CNN-based model and 20% and 99% for the CNN-based model. The performance of the CNN-based model did not improve with a mask layer guiding the model's attention towards the conjunctival regions, however, slightly improved with correction by the aspect ratio and exposure time of input images. The gradient-weighted class activation mapping heatmap indicated that the lower half area of the conjunctiva was crucial for haemoglobin value prediction. In conclusion, the CNN-based model had better results than the non-CNN-based model. The prediction accuracy would improve by using more input data with anaemia.

Successful treatment of young childhood standard-risk hepatoblastoma with cisplatin monotherapy using a central review system.

BACKGROUND: The JPLT3-S (Japanese Study Group for Pediatric Liver Tumors-3) study, conducted cisplatin (CDDP) monotherapy for young children (<3 years old) with standard-risk hepatoblastoma (HB) using a central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT (PRETreatment EXTent of disease) classification (standard-risk HB) showed favorable outcomes with treatment consisting of CDDP and pirarubicin, but showed toxicities and late complications. In the JPLT3-S trial, a less intense regimen consisting of CDDP alone was evaluated. METHODS: Patients who were less than 3 years of age and with PRETEXT I, II, or III HB without any annotation factors (e.g., E1, E1a, E2, E2a, H1, N1, P2, P2a, V3, and V3a) were eligible for inclusion in this study. In this trial, the central radiological and pathological features of all patients were reviewed. The primary outcome was the 3-year progression-free survival (PFS). RESULTS: A total of 38 patients (23 female) were included. The median patient age was 12 months (range: 2-34). Two patients discontinued treatment because of progressive disease, and five patients discontinued treatment for other reasons. The 3-year PFS rate was 93.9% (95% confidence interval [CI]: 86.4%-100%). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (CI: 100). Eighteen of the 38 patients (47.4%) experienced ototoxicity as a late complication. CONCLUSION: CDDP monotherapy regimen is feasible in young patients with localized HB, as classified by a central review.

Diuretic and renal effects of angiotensin receptor-neprilysin inhibitor in patients hospitalized for acute heart failure.

In patients hospitalized for acute decompensation of heart failure (HF), the impact of angiotensin receptor-neprilysin inhibitor (ARNI) on diuresis and renal function has not been fully investigated. Patients with HF and reduced ejection fraction who were hospitalized for acute decompensation and newly initiated ARNI after hemodynamic stabilization were enrolled. Changes in urine volume (UV), body weight, estimated glomerular filtration rate (eGFR), and urine N-acetyl-beta-d-glucosaminidase (uNAG) levels before and after ARNI initiation were investigated. Changes in the diuretic response [DR, calculated as urine volume/(intravenous furosemide volume/40 mg)], N-terminal pro-brain natriuretic peptide (NT-proBNP), hematocrit, and plasma volume (PV) were also evaluated. A total of 60 patients were enrolled. ARNI was initiated at a median of 6 [5, 7] days after hospitalization. After initiation of ARNI, body weight, NT-proBNP, and PV decreased. UV and DR increased only on the day of ARNI initiation (delta UV 400 ± 957 ml and delta DR 1100 ± 3107 ml/40 mg furosemide) and then decreased to baseline levels. In the multivariable linear regression analysis, younger age, higher BMI, and higher NT-proBNP levels were significantly associated with greater UV after ARNI initiation. eGFR and uNAG did not significantly change after the initiation of ARNI [delta eGFR -1.7 ± 12.0 mL/min/1.73 m2 and delta uNAG 2.0 (-5.6, 6.9) IU/L]. In patients hospitalized for HF, the initiation of ARNI was associated with a small and transient increase in UV and DR, and was not associated with worsening of renal function or tubular injury.

[Delayed diagnosis of hydroa vacciniforme-like lymphoproliferative disorder in a patient with skin rashes].

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent EBV infection and can lead to fatal conditions such as hemophagocytic syndrome and malignant lymphoma through the clonal expansion of EBV-infected T or natural killer (NK) cells. Hydroa vacciniforme lymphoproliferative disorder (HV) and hypersensitivity to mosquito bites (HMB) have been identified as skin diseases in EBV-associated T- or NK-cell lymphoproliferative diseases. We present the case of a 33-year-old man. The patient had frequent episodes of a facial rash for three years before he visited our hospital, he visited several dermatologists but did not receive a diagnosis of HV. He was referred to the hematology department of our hospital for assessment of atypical lymphocytes in peripheral blood. Based on routine blood and bone marrow test we were unable to diagnose HV. However, when the patient's liver function deteriorated six months later, we considered the possibility of HV after reevaluating the skin rash. After performing EBV-related tests, we were able to definitively diagnose CAEBV with HV. It is crucial to be able to connect clinical observations to EBV-related tests when diagnosing CAEBV. Hematologists must be knowledgeable of the EBV-associated skin conditions of HV and HMB.

Low NUDT15 expression levels due to biallelic NUDT15 variants and 6-mercaptopurine intolerance.

6-Mercaptopurine (6-MP) is widely used for the treatment of paediatric leukaemia and lymphoma. Recently, germline variants in the NUDT15 gene have been identified as one of the major genetic causes for 6-MP-associated adverse effects such as myelosuppression. Patients with hypomorphic NUDT15 variants accumulate excessive levels of DNA-incorporated thioguanine in white blood cells, resulting in severe myelosuppression. Although preclinical studies suggest that these variants may influence the protein stability of NUDT15, this has not been directly characterised in patients. In this study, we report the development of a series of novel monoclonal antibodies against NUDT15, using which we quantitatively assessed NUDT15 protein levels in 37 patients with acute lymphoblastic leukaemia treated with 6-MP, using sandwich enzyme-linked immunosorbent assay (ELISA). The NUDT15 genotype was highly correlated with its protein levels (p < 0.0001), with homozygous and compound heterozygous patients showing exceedingly low NUDT15 expression. There was a positive correlation between NUDT15 protein level and 6-MP tolerance (r = 0.631, p < 0.0001). In conclusion, our results point to low NUDT15 protein abundance as the biochemical basis for NUDT15-mediated 6-MP intolerance, thus providing a phenotypic readout of inherited NUDT15 deficiency.

Malnutrition, hemodynamics and inflammation in heart failure with reduced, mildly reduced and preserved ejection fraction.

In patients with heart failure (HF) with reduced ejection fraction (HFrEF), malnutrition can be associated with intestinal congestion and systemic inflammation. These relationships have not been fully investigated in HF with mildly reduced EF (HFmrEF) and with preserved EF (HFpEF). We analyzed 420 patients with HF who underwent right heart catheterization. The relationships between hemodynamic parameters, C-reactive protein, and the controlling nutritional (CONUT) score were investigated in HFrEF, HFmrEF and HFpEF. The CONUT score of all patients was 2 [1, 4] (median [interquartile range]), and was not significantly different between the left ventricular EF (LVEF) categories (2 [1, 3] for HFrEF, 2 [1, 3] for HFmrEF, and 3 [1, 4] for HFpEF, p = 0.279). In multivariate linear regression analyses, there was a significant association between CRP and the CONUT score in HFmrEF and HFpEF, while brain natriuretic peptide and right atrial pressure were significantly associated with the CONUT score in HFrEF. Higher CONUT scores predicted a higher incidence of the composite endpoint of death or HF hospitalization within 12 months without an interaction with LVEF (p = 0.980). The CONUT score was an independent predictor of the composite endpoint, death, and HF hospitalization after adjustment for confounders in the multivariate analysis. In conclusion, inflammation was associated with malnutrition in HFmrEF and HFpEF, while congestion was an independent predictor of malnutrition in HFrEF. Malnutrition predicted worse outcomes regardless of LVEF.

KMT2A-rearranged diffuse large B-cell lymphoma in a child: a case report and molecular characterization.

KMT2A-rearranged diffuse large B-cell lymphoma (DLBCL) is rare in both the adult and pediatric populations, and its biological features are unclear. We here report the case of a 19-month-old female with a right temporal bone tumor that was ultimately diagnosed as DLBCL by tumor biopsy. There was no morphological evidence of bone marrow infiltration at diagnosis. The tumor nearly completely dissolved after scheduled chemotherapy for mature B-cell lymphoma; however, leukemic conversion occurred 2 months after completion of chemotherapy. Additional chemotherapy including hematopoietic cell transplantation in a non-remission state was unsuccessful, and disease progression ultimately resulted in the death of the patient 18 months after the diagnosis. We detected the KMT2A-MLLT3 fused transcript in the bone marrow of the patient with primary and recurrent cancer. RNA-sequencing of the bone marrow with recurrent cancer confirmed the KMT2A-MLLT3 fusion gene, although fusion genes involving BCL6, BCL2, or were not detected. Moreover, RNA-sequencing revealed overexpression of MEIS1 and MEF2C, which are highly expressed in KMT2A-rearranged leukemia, whereas the HOXA gene cluster was not overexpressed. The current case formed part of the KMT2A-rearranged acute lymphoblastic leukemia cluster in a T-distributed stochastic neighbor embedding plot. The aggressive clinical course and RNA-sequencing results of the present case suggest that KMT2A-rearranged DLBCL shares biological features with KMT2A-rearranged leukemia.

Evaluation of changes in oral health-related quality of life over time in patients with Sjögren's syndrome.

OBJECTIVES: To assess oral health-related quality of life (OHRQoL) and changes in OHRQoL in 3 years of patients with Sjögren's symdrome (SS). METHODS: Thirty-five SS patients and 23 non-SS individuals were enrolled. OHRQoL were quantitatively evaluated using the shortened Oral Health Impact Profile (OHIP-14). After 3 years, 22 patients and 14 controls tool the OHIP-14 survey again. RESULTS: The SS group had a significantly higher OHIP-14 score, which indicated a lower OHRQoL, than the non-SS group. Among individual questions in the OHIP-14, scores for 'trouble pronouncing words', 'uncomfortable to eat foods', 'self-conscious', and 'diet unsatisfactory' were markedly higher in the SS group than in the non-SS group. The OHIP-14 score significantly increased in 3 years in the SS group. Furthermore, there was an inverse correlation between the change rate of salivary flow rate and change of OHIP-14 scores in 3 years in patients with SS whose OHIP-14 score increased. Scores for 'irritable with other people', 'difficulty doing usual jobs', 'felt life less satisfying', and 'unable to function' significantly increased in 3 years. CONCLUSION: In SS, OHRQoL decreased in 3 years, which was associated with a decrease in saliva secretion. Moreover, troubles related to psychosocial aspects in SS patients were found to intensify over time.

A case of malignant rhabdoid tumor mimicking yolk sac tumor.

Malignant rhabdoid tumors (MRTs) are rare, highly aggressive embryonal neoplasms caused by biallelic alterations of the SMARCB1 gene. MRTs may occur in any soft tissue, but extracranial extrarenal MRTs are extremely rare. Diagnosis of MRTs in unusual locations and with an uncharacteristic cytomorphology that mimics other tumors is difficult. This was an atypical case of MRT in a 15-year-old female with tumors that closely resembled yolk sac tumors. It was extremely challenging to diagnose the tumors without confirming the SMARCB1 status.

Relationship between YKL-40 and pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an intractable connective tissue disease that causes skin and organ fibrosis. Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) affect its prognosis. YKL-40 protein impacts inflammation and tissue remodeling. Therefore, we evaluated the utility of YKL-40 blood levels in identifying patients with SSc complicated by PAH, as confirmed by immunohistochemistry (IHC) examination. METHODS: We retrospectively analyzed 78 patients with SSc and performed IHC on 7 normal and 7 SSc skin samples in the Japanese population. Age-adjusted YKL-40 serum levels were analyzed. RESULTS: YKL-40 age percentile was significantly elevated in SSc patients. There was no difference between patients with SSc with and without ILD and PAH. YKL-40 age percentile was greater in patients with PAH complication. YKL-40 immunostaining was negative in normal skin and prominent in the subcutaneous vascular wall of all SSc samples. Receiver operating characteristic (ROC) curve analysis indicated that YKL-40 age percentile correctly differentiated between patients with and without PAH with a sensitivity of 80% and a specificity of 94.1%. CONCLUSION: A higher YKL-40 level with PAH may be reflective of angiogenesis due to capillary injury in SSc. YKL-40 may offer a useful and easily applicable diagnostic biomarker of SSc complicated with PAH.

Predictive factors for structural remission using abatacept: Results from the ABROAD study.

OBJECTIVE: To investigate the effect of abatacept (ABA) on preventing joint destruction in biological disease-modifying anti-rheumatic drug (bDMARD)-naïve rheumatoid arthritis (RA) patients in real-world clinical practice. PATIENTS AND METHODS: RA patients were collected from the ABROAD (ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD) study cohort. They had moderate or high disease activity and were treated with ABA as a first-line bDMARD. Radiographic change between baseline and 1 year after ABA treatment was assessed with the van der Heijde's modified Total Sharp Score (mTSS). Predictive factors for structural remission (St-REM), defined as ΔmTSS ≤0.5/year, were determined. RESULTS: Among 118 patients, 81 (67.5%) achieved St-REM. Disease duration <3 years (odds ratio (OR) = 3.152, p = .007) and slower radiographic progression (shown as 'baseline mTSS/year <3', OR = 3.727, p = .004) were independently significant baseline predictive factors for St-REM irrespective of age and sex. St-REM prevalence increased significantly if clinical remission based on the Simplified Disease Activity Index was achieved at least once until 24 weeks after ABA treatment. CONCLUSION: Shorter disease duration, smaller radiographic progression at baseline, and rapid clinical response were predictive factors for sustained St-REM after ABA therapy in bDMARD-naïve RA patients.

Tackler's head position relative to the ball carrier is highly correlated with head and neck injuries in rugby.

OBJECTIVES: To characterise the tackler's head position during one-on-one tackling in rugby and to determine the incidence of head, neck and shoulder injuries through analysis of game videos, injury records and a questionnaire completed by the tacklers themselves. METHODS: We randomly selected 28 game videos featuring two university teams in competitions held in 2015 and 2016. Tackles were categorised according to tackler's head position. The 'pre-contact phase' was defined; its duration and the number of steps taken by the ball carrier prior to a tackle were evaluated. RESULTS: In total, 3970 tackles, including 317 (8.0%) with the tackler's head incorrectly positioned (ie, in front of the ball carrier) were examined. Thirty-two head, neck or shoulder injuries occurred for an injury incidence of 0.8% (32/3970). The incidence of injury in tackles with incorrect head positioning was 69.4/1000 tackles; the injury incidence with correct head positioning (ie, behind or to one side of the ball carrier) was 2.7/1000 tackles. Concussions, neck injuries, 'stingers' and nasal fractures occurred significantly more often during tackles with incorrect head positioning than during tackles with correct head positioning. Significantly fewer steps were taken before tackles with incorrect head positioning that resulted in injury than before tackles that did not result in injury. CONCLUSION: Tackling with incorrect head position relative to the ball carrier resulted in a significantly higher incidence of concussions, neck injuries, stingers and nasal fractures than tackling with correct head position. Tackles with shorter duration and distance before contact resulted in more injuries.

Anticentromere antibody-positive primary Sjögren's syndrome: Epitope analysis of a subset of anticentromere antibody-positive patients.

OBJECTIVES: Anticentromere antibody (ACA) is generally considered to be a serological marker for systemic sclerosis (SSc). ACA-positive patients with primary Sjögren's syndrome (pSS) have also been reported. ACA often recognizes centromere proteins (CENPs): CENP-A, CENP-B, and CENP-C, and sometimes reacts to heterochromatin protein 1 (HP1)α. We compared the reactivity against six different epitopes for three ACA-positive clinical subgroups: 29 patients with pSS, 36 SSc patients with sicca symptoms, and 28 SSc patients without sicca symptoms. METHODS: We utilized enzyme-linked immunosorbent assays (ELISAs) with recombinant proteins covering six different epitope regions of ACA (the amino terminus (Nt) of CENP-A, CENP-B, and CENP-C, the carboxyl terminus (Ct) of CENP-B and CENP-C, and HP1α). RESULTS: The patients with pSS were found to have IgG-class autoantibodies against CENP-C-Nt and HP1α, and IgA-class autoantibodies against CENP-C-Ct with significantly higher frequencies than the SSc patients with or without sicca symptoms. The positive predictive value and the negative predictive value of the combination of these three autoantibodies for pSS were 73% and 82%, respectively, for pSS. CONCLUSIONS: Based on the result that reactivities against CENP-C and HP1α in patients with pSS differ from those in patients with SSc, we propose ACA-positive pSS as a clinical subset of SS that is independent of SSc.

Systemic lupus erythematosus presenting with mixed-type fulminant autoimmune hemolytic anemia.

We report the case of a 9-year-old girl who presented with mixed-type fulminant autoimmune hemolytic anemia (AIHA) at the onset of systemic lupus erythematosus (SLE). On admission, laboratory investigations indicated very severe anemia (Hb, 2.7 g/dL) with reticulocytosis and positive direct/indirect Coombs tests. In addition, agglutinative reaction was clinically observed. Based on further examinations, the patient was diagnosed with AIHA complicated with SLE, and mixed-type AIHA was clinically identified. With oral prednisolone and methylprednisolone pulse therapy, the patient entered remission.

Rapid decrease in salivary epidermal growth factor levels in patients with Sjögren's syndrome: A 3-year follow-up study.

OBJECTIVES: To assess changes in salivary epidermal growth factor (EGF) levels within three years and investigate the correlation between these changes and the severity of intraoral manifestations in patients with Sjögren's syndrome (SS). METHODS: Twenty-three SS patients (14 primary SS and 9 secondary SS) and 14 controls were followed up for three years. Salivary EGF concentration was measured using an enzyme-linked immunosorbent assay, and intraoral manifestations were evaluated using a short version of the Oral Health Impact Profile (OHIP-14). Changes in salivary flow rate, EGF level, and severity of intraoral manifestations were analyzed, along with associations among them. RESULTS: The OHIP-14 score significantly increased and the total salivary EGF output significantly decreased after three years in the SS group (10.2 ± 8.8 vs. 12.6 ± 9.2, p = 0.040; 10158.4 ± 9820.9 vs. 8352.8 ± 7813.3 pg/10 min, p = 0.032), though the salivary flow rate did not change. The decrease in total EGF output was especially high in patients with long disease duration and poor oral health-related quality of life (OHRQoL). In patients with poor OHRQoL, the change in total EGF output significantly correlated with the OHIP-14 score (r = - 0.847, p = 0.008). However, there was no correlation between the change in salivary flow rate and the OHIP-14 score. CONCLUSIONS: The rapid decrease in salivary EGF level contributes to the progression of intraoral manifestations of SS.