Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.

OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.

Functional reconstruction of elbow flexion with latissimus dorsi muscle rotational transfer: two case reports.

BACKGROUND: We report two cases of biceps brachii and brachialis paralysis due to musculocutaneous nerve injury in which elbow joint flexion was reconstructed using rotational transfer of the latissimus dorsi muscle with sutures to the radial and ulnar tuberosities, thereby enabling flexion by simultaneous activation of the humeroradial and humeroulnar joints. In cases of associated brachialis paralysis, weaker flexion strength can be expected when the forearm is in a pronated position than when it is in a supinated state. To the best of our knowledge, no previous study has reported the rotational position of the forearm during elbow joint flexion reconstruction. CASE PRESENTATION: Case 1 involved a 30-year-old Asian male who presented with a rupture of the musculocutaneous, median, radial, and ulnar nerves. Reconstruction was performed by rotational transfer of the latissimus dorsi muscle. In this case, the supination and pronation flexion forces were equal. Case 2 involved a 50-year-old Asian man who presented with partial loss of the musculocutaneous nerve, biceps brachii, and pectoralis major due to debridement. Reconstruction was performed by rotational transfer of the latissimus dorsi muscle. In this case, supination and pronation flexion strengths were demonstrated to be equal. Our reconstruction method used the rotational transfer of the latissimus dorsi muscle; the distal muscle flap was divided into radial and ulnar sides to allow elbow joint flexion by simultaneously activating the humeroradial and humeroulnar joints. These sides were then fixed to the anchors at the radial and ulnar tuberosities. Finally, they were wrapped around the myotendinous junction of the biceps brachii or brachialis and secured using sutures. CONCLUSIONS: Although larger studies are required to verify these methods, this case study successfully demonstrates the following: (1) the flexion strength in the supinated position was equal to that in the pronated position; (2) the stability of the humeroradial and humeroulnar joints was unaffected by the forearm's rotational position; and (3) a satisfactory range of motion of the elbow joint was obtained, with no complications.

Open Reduction and Internal Fixation of Dorsal Fracture-Dislocation of the Proximal Interphalangeal Joint Using a Plate: A Series of 37 Patients.

Background: Open reduction and internal fixation with a plate is one of the alternative treatments for fracture-dislocation of the proximal interphalangeal (PIP) joint. However, it does not always lead to satisfactory results. The aim of this cohort study is to describe the surgical procedure and discuss the factors affecting the treatment results. Methods: We retrospectively reviewed 37 cases of consecutive unstable dorsal fracture-dislocation of the PIP joint treated using a mini-plate. The volar fragments were sandwiched with a plate and dorsal cortex, and screws were used as subchondral support. The average rate of articular involvement was 55.5%. Five patients had concomitant injuries. The mean age of the patients was 40.6 years. Mean time between injury and operation was 11.1 days. The average postoperative follow-up duration was 11 months. Active ranges of motion, % total active motion (TAM) were evaluated postoperatively. The patients were divided into two groups according from Strickland score and Gaine score. Fisher's exact test, Mann-Whitney U test and a logistic regression analysis were used to evaluate the factors affecting the results. Results: The average active flexion, flexion contracture at the PIP joint, and % TAM were 86.3°, 10.5° and 80.6%, respectively. Group I included 24 patients who had both excellent and good scores. Group II included 13 patients who had neither excellent nor good scores. When the groups were compared, there was no significant relationship between the type of fracture-dislocation and the extent of articular involvement. There were significant associations between outcomes and patient age, period from injury to surgical intervention and presence of concomitant injuries. Conclusions: We concluded that meticulous surgical technique leads to satisfactory results. However, factors, including the patient's age, time from injury to surgery and the presence of concomitant injuries needing adjacent joint immobilisation, contribute to unsatisfactory outcomes. Level of Evidence: Level IV (Therapeutic).

Decreased expression of airway epithelial Axl is associated with eosinophilic inflammation in severe asthma.

BACKGROUND: Airway epithelium-derived cytokines are critical to provoke and perpetuate type 2 inflammation in asthma. Yet it is poorly understood how this epithelial cell-driven inflammatory response is negatively regulated. We previously reported that Axl receptor tyrosine kinase was expressed by basal cells in the airway epithelium and had a role in defining their stem cell identity. However, whether and how Axl regulates airway type 2 inflammation remains unknown. METHODS: We performed immunofluorescence staining to compare Axl expression in airway epithelium between non-asthmatic subjects, mild-moderate asthma and severe asthma. We confirmed this result by interrogating public databases of global gene expression in endobronchial biopsies. We then quantified eosinophil numbers infiltrating into the trachea of wild-type or Axl-knockout mice that were intranasally treated with house dust mite extracts (HDM). Cell-based assays using siRNA targeting Axl were further performed to identify molecules involved in Axl-mediated regulation of inflammation. RESULTS: Histological assessments and transcriptome analyses revealed decreases in protein and mRNA of Axl in airway basal cells of severe asthmatics. This reduction of Axl expression was correlated with infiltration of eosinophils and mast cells in severe asthmatics. Eosinophil infiltration was more evident in the trachea of Axl-knockout mice in response to repetitive HDM administration. siRNA-mediated knockdown of Axl increased mRNA and protein expression of granulocyte macrophage-colony stimulating factor (GM-CSF) in human bronchial epithelial cells. CONCLUSIONS: Axl kinase expressed by basal cells may suppress excessive eosinophilic inflammation via inhibition of GM-CSF in the airway. Axl reduction has clinical implications for the pathogenesis of severe asthma.

Using blood glucose and lactate levels for early detection of venous congestion following a free flap procedure for lower extremity open fractures.

PURPOSE: Gustilo-Anderson type IIIB and IIIC open fractures of the lower extremities require reconstruction of extensively injured soft tissues using a free flap; however, impaired blood flow through the flap is an early postoperative complication. To detect flap congestion due to venous thrombosis, blood glucose and lactate level measurements within the flap are taken to determine variations in these levels. We aimed to detect early-stage venous congestion and to perform salvage operations. METHODS: We included 22 limbs with lower leg and foot open fractures, with fracture sites covered using a free flap. A pinprick test was used to measure blood glucose and lactate levels. RESULTS: Of 7 and 15 congested and non-congested limbs, respectively, the 7 congested limbs had a mean flap blood glucose level immediately before salvage surgery of 3.8 ± 2.0 (7.4-1.8) mmol/L. The ratio to blood glucose levels in healthy fingertips was 0.6 ± 0.2 (0.8-0.3). Lactate levels increased to 13.3 ± 5.1 (9.4-22.8) mmol/L. The ratio of blood glucose levels in congested flaps and in healthy fingertips was significantly lower than that in non-congested flaps and in healthy fingertips (p = 0.0016). Lactate levels were significantly higher in patients with congestion (p = 0.0013). Salvage surgery was performed, thrombi were removed, and six limb flaps were viable. CONCLUSION: Flap blood glucose and lactate levels provide a quantitative method of evaluating blood flow and detecting flow abnormalities postoperatively, and are useful in detecting early congestion due to venous thrombosis.

Cutaneous methotrexate-related T-cell lymphoproliferative disorder with CD4, CD30, CD56, EBV-positive tumor cell infiltration: a case illustration and a brief review.

Methotrexate (MTX) is a commonly used anti-metabolite agent. Long-term MTX treatment can cause MTX-related lymphoproliferative disorder (MTX-LPD). T-cell LPDs comprise a small fraction of MTX-LPDs. Epstein-Barr virus (EBV)+ tumor cells are rarely detected in MTX-related T-cell LPDs (MTX T-LPDs). Therefore, there have been very few reports of EBV+ MTX T-LPD. We encountered a case of cutaneous MTX T-LPD with a unique cellular phenotype. The patient was a 71-year-old Japanese man with rheumatoid arthritis treated with MTX for 6 years. He was referred to our department with a 6-month history of red plaques and ulcerated lesions in both lower legs and a 2-week history of high fever and fatigue. Cutaneous specimens showed that medium-sized atypical lymphocytes were positive for CD3, CD4, CD30, CD56, and in situ hybridization for EBV-encoded RNA. The patient was diagnosed with cutaneous MTX T-LPD. Four months after discontinuation of MTX, the skin lesions had disappeared. This is the first report of cutaneous MTX T-LPD with CD4+CD30+CD56+EBV+ tumor cells.

Diffuse cutaneous mastocytosis: Identification of KIT mutation and long-term follow-up with serum tryptase level.

Diffuse cutaneous mastocytosis (DCM) is the least common subtype of cutaneous mastocytotis and is generally more severe than other subtypes. We herein report a case of DCM with the consequence of a long-term follow-up. A 4-month-old boy visited with a 3-month history of diffuse erythema that gradually worsened. Darier's sign was positive. The plasma histamine level was 4.95 ng/mL, and the serum tryptase and c-Kit (CD117) levels were 33.3 and 27.4 ng/mL, respectively. Histopathology of the biopsied specimen showed dermal papillary edema and infiltration of mast cells identified by c-Kit and toluidine blue staining. Amplification and direct sequencing of genomic DNA extracted from the skin biopsy specimen revealed the presence of a deletion of codon 419 in exon 8 (c.1255_1257delGAC [p. Asp419del]). There was no evidence of systemic infiltration of mast cells in this case, and we started topical corticosteroid and oral antihistamine with the diagnosis of DCM. Diffuse erythema subsided constantly with age in parallel with chronological decline of serum tryptase level, and it is no longer apparent presently at the age of 7 years, leaving only faint brown spots. Blister formation did not occur throughout the course. Our case indicates that spontaneous resolution can be expected even in DCM after a long period of time, and that serum tryptase level serves as a good surrogate marker to monitor the clinical course.

Painful Snapping of Thumb Caused by a Displaced Non-Union Fragment from the Trapezium: A Case Report.

There are only a few reports regarding snapping thumb caused by the pathology of the extensor tendon. We report a rare case of snapping thumb caused by a displaced non-union fragment from the trapezium in a 54-year-old man treated with the surgical resection. The intraoperative findings and the outcome are described.

Flexor Tendon Avulsion Injury Associated with Distal and Proximal Phalanx Fracture: A Case Report.

We present an extremely rare case of avulsion injury of the flexor digitorum profundus and the flexor digitorum superficialis tendons associated with fracture of the distal phalanx and bone bruise of the proximal phalangeal base of the small finger. Because of the nondisplaced transverse fracture of the distal phalanx, the early diagnosis of the injury was missed. The patient was treated with two-stage flexor tendon graft and the outcome was acceptable.

Features of and preventive measures against hypertension in the young.

The Japanese hypertension guidelines report that essential hypertension is detected in 1-3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged <40 years should be educated about the association between body weight and hypertension. Particular caution surrounding lifestyle habits, including drinking and smoking, is warranted in male hypertensive subjects because hypertension at a young age is strongly associated with obesity. BP monitoring and the management of obesity should be considered efficient approaches to the detection and treatment of hypertension. For the lifetime prevention of hypertension, it is essential to be aware of one's health status and learn about healthy lifestyles beginning in childhood. BP measurement may be an appropriate means to achieve this goal.

Morning Home Blood Pressure and Cardiovascular Events in Japanese Hypertensive Patients.

SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated the benefit of achieving strict blood pressure control with a lower target blood pressure level in high-risk patients with hypertension. The aim of this post hoc analysis was to investigate the relationship between the 2-year average on-treatment home blood pressure and cardiovascular disease risk in subgroups stratified by risk status using data from the HONEST study (Home Blood Pressure Measurement With Olmesartan Naive Patients to Establish Standard Target Blood Pressure). Participants in the HONEST study (n=21 591) were stratified according to risk level as follows: SPRINT population (n=5823)-patients (≥50 years of age) without diabetes mellitus or prior stroke, with SPRINT-defined cardiovascular risk and systolic blood pressure (SBP) of ≥130 mm Hg; SPRINT-excluded high-risk population (n=5481)-patients with diabetes mellitus or prior stroke; and non-SPRINT low-risk population-all other patients in the HONEST study (n=10 287). Cardiovascular disease event risk was 6.32 events per 1000 person-years in the SPRINT population, which was higher than in the non-SPRINT low-risk (3.39; P<0.001) and lower than the SPRINT-excluded high-risk (12.41; P<0.001) populations. In the SPRINT and the SPRINT-excluded high-risk populations, a lower home SBP achieved was associated with lower cardiovascular disease risk, with the lowest risk in patients with a home SBP <125 mm Hg. The non-SPRINT low-risk population showed a J-curve association between on-treatment home SBP and cardiovascular disease risk with the lowest risk at a home SBP of 135 to <145 mm Hg. Intensive therapy targeting home SBP of <125 mm Hg would be beneficial for high-risk hypertensive patients. Clinical Trial Registration- URL: http://www.umin.ac.jp/ctr/index.htm . UMIN Clinical Trials Registry, trial no.: UMIN000002567.

Case report: retroperitoneal aspergilloma in a patient with rheumatoid arthritis presenting as malignant tumor.

BACKGROUND: Aspergillosis in patients with impaired immunity usually presents with invasive pulmonary infection and dissemination to a variety of organs via hematogenous spread. Aspergilloma in the retroperitoneal cavity is a rare disease with only a few cases reported in the literature. To the best of our knowledge, the present case of a retroperitoneal aspergilloma with no surgical history is only the second report in the literature. CASE PRESENTATION: A 65 year-old man, who had been receiving immunosuppressive treatment for rheumatoid arthritis with vasculitis for 9 years, was referred to the Urology Department with a retroperitoneal mass. This was confirmed by computed tomography performed during treatment for pulmonary aspergilloma. Because it was not possible to rule out malignant disease (e.g., liposarcoma), surgical exploration was performed. Pathological examination revealed aspergillus hyphae with fat necrosis, and retroperitoneal aspergilloma was diagnosed and appropriately treated. The tumor did not recur subsequently. CONCLUSION: Our present case emphasizes that pharmacological treatments for aspergilloma in the retroperitoneal cavity have poor drug transitivity, so the relative effectiveness of pharmacological response is not useful for differentiating retroperitoneal aspergilloma from malignant disease.

Home blood pressure and cardiovascular outcomes in very elderly patients receiving antihypertensive drug therapy: a subgroup analysis of Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study.

The appropriate target blood pressure (BP) in elderly patients with hypertension remains uncertain. We investigated the relationship between morning home systolic blood pressure (MHSBP) during follow-up and cardiovascular (CV) risk in outpatients receiving olmesartan-based treatment aged <75 years (n = 16799) and ≥75 years (n = 4792) in the HONEST study. In the follow-up period (mean 2.02 years), the risk for major CV events was significantly higher in patients with MHSBP ≥155 mmHg compared with <125 mmHg in both age groups in Cox proportional hazards model adjusted for other risk factors and there was no significant difference in trend between the two groups (interaction P = 0.9917 for MHSBP). Hazard ratios for CV events for 1-mmHg increase in MHSBP were similar in patients aged <75 years and in patients aged ≥75 years. The incidence of adverse drug reactions related to excessive BP lowering was lower in patients <75 years than in patients ≥75 years (0.73 vs 1.02%, P = 0.0461). In conclusion, the study suggests even in patients ≥75 years antihypertensive treatment targeting the same MHSBP levels in patients <75 years may be beneficial in reducing CV risk when treatment is tolerated.

Increased cardiovascular risk of treated white coat and masked hypertension in patients with diabetes and chronic kidney disease: the HONEST Study.

The prognostic implications of treated white coat hypertension (WCH) and masked hypertension (MH) in patients with diabetes mellitus (DM) or chronic kidney disease (CKD) are not well documented. Using data from the HONEST study (n=21 591), we investigated the relationships between morning home systolic blood pressure (MHSBP) or clinic systolic blood pressure (CSBP) and cardiovascular (CV) risk in hypertensive patients with and without DM or CKD receiving olmesartan-based antihypertensive therapy. The study included 4426 DM patients and 4346 CKD patients at baseline who had 101 and 87 major CV events, respectively, during the follow-up. Compared with well-controlled non-DM patients (MHSBP <135 mm Hg; CSBP <140 mm Hg), DM patients with WCH (MHSBP <135 mm Hg; CSBP ⩾140 mm Hg), MH (MHSBP ⩾135 mm Hg; CSBP <140 mm Hg) or poorly controlled hypertension (PCH) (MHSBP ⩾135 mm Hg; CSBP ⩾140 mm Hg) had significantly higher CV risk (hazard ratio (HR), 2.73, 2.77 and 2.81, respectively). CV risk was also significantly increased in CKD patients with WCH, MH and PCH (HR, 2.14, 1.70 and 2.20, respectively) compared with well-controlled non-CKD patients. Furthermore, DM patients had significantly higher incidence rate than non-DM patients of MHSBP ⩾125 to <135 mm Hg (HR, 1.98) and ⩾135 to <145 mm Hg (HR, 2.41). In conclusion, both WCH and MH are associated with increased CV risk, and thus control of both MHSBP and CSBP is important to reduce CV risk in DM or CKD patients. The results also suggest that even lower MHSBP (<125 mm Hg) may be beneficial for DM patients, although this conclusion is limited by the small number of patients.