Inflammatory CD11b+ Macrophages Produce BAFF in Spleen of Mice Infected with Leishmania donovani.

Visceral leishmaniasis (VL) is an infectious disease caused by parasitic protozoa of the genus Leishmania and manifests clinical symptoms such as splenomegaly, hepatomegaly, anemia, and fever. It has previously been shown that B-cell-activating factor (BAFF) is involved in splenomegaly during VL. Although BAFF is known to be expressed by a variety of cells, the mechanism of elevated BAFF expression in VL is not clear. In this study, we aimed to identify BAFF-producing cells in the spleens of mice infected with Leishmania donovani. Splenocytes of L. donovani-infected mice showed elevated BAFF expression compared to that of naive mice. In the infected spleen, the number of both CD11b+ and F4/80+ cells increased, and the major BAFF-producing cells were CD11b+ cells, which did not serve as host cells of Leishmania. Immunohistochemical/immunofluorescent staining of spleens of infected mice revealed that the increased CD11b+ cells were primarily MRP14+ mononuclear cells. Together, these results suggest the increased BAFF expression in the spleen of L. donovani-infected mice involves a recruitment of inflammatory macrophages distinct from host macrophages for the parasites.

Frontiers of Collaboration between Primary Care and Specialists in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Review.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common liver disease. It has a rapidly growing patient population owing to the increasing prevalence of obesity and type 2 diabetes. Patients with MASLD are primarily treated by family physicians when fibrosis is absent or mild and by gastroenterologists/hepatologists when fibrosis is more advanced. It is imperative that a system for the appropriate treatment and surveillance of hepatocellular carcinoma be established in order to ensure that highly fibrotic cases are not overlooked among the large number of MASLD patients. Family physicians should check for viral hepatitis, autoimmune hepatitis, alcoholic liver disease, and drug-induced liver disease, and should evaluate fibrosis using NIT; gastroenterologists/hepatologists should perform liver biopsy, ultrasound elastography (260 units in Japan as of October 2023), and MR elastography (35 units in Japan as of October 2023). This review presents the latest findings in MASLD and the role, accuracy, and clinical use of NIT. It also describes the collaboration between Japanese primary care and gastroenterologists/hepatologists in Japan in the treatment of liver diseases, including MASLD.

Solitary juvenile polyp of the rectum with intramucosal adenocarcinoma.

We describe a case of solitary juvenile polyp of the rectum with intramucosal adenocarcinoma. A 55-year-old man presented to our hospital for evaluation after a positive fecal occult blood test. Colonoscopy revealed a pedunculated polyp of 25 mm in size which has an irregular shape and pale red color on the rectum. The polyp had a proliferation of blood vessels and an invisible surface pattern. Endoscopic mucosal resection was performed. Pathologically, it was diagnosed as a solitary juvenile polyp with intramucosal well-differentiated adenocarcinoma. When we encounter juvenile polyps, the possibility of malignancy should be taken into consideration for treatment.

Comparison of the 2-Year Results of Photodynamic Therapy with Aflibercept and Aflibercept Monotherapy for Polypoidal Choroidal Vasculopathy.

Purpose: To compare the efficacies of photodynamic therapy (PDT) combined with intravitreal aflibercept (IVA) injections and IVA monotherapy using a treat-and-extend regimen (TAE) for treatment-naïve polypoidal choroidal vasculopathy (PCV). Patients and Methods: One hundred and nine eyes treated with PDT combined with IVA (PDT+IVA group: 51 eyes) or IVA monotherapy (IVA group: 58 eyes) were assessed for 2 years. The main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of IVA injections, and macular atrophy (MA). Polypoidal lesions before and after the loading phase were assessed using indocyanine green angiography. Results: In both groups, BCVA significantly improved after the loading phase and was maintained for 2 years. CMT and CCT were significantly reduced in both groups, without significant differences after 2 years between the groups (P=0.2708). The mean number of IVA injections in the IVA and PDT+IVA groups during the 2 years were 13.2±3.3 and 12.7±1.8, respectively, without a significant difference (P=0.06). The frequencies of MA expansion in the IVA and PDT+IVA groups during the 2 years were 25.9% and 33.4%, respectively, with no significant difference in the incidence (odds ratio: 1.40, P=0.4253). The ratios of polyp regression after the loading phase in the IVA and PDT+IVA groups were 55.2% and 94.1%, respectively, with a significant difference (P<0.0001). Conclusion: PDT combined with IVA injections using a TAE regimen is effective for anatomical and visual function improvement, without a significant difference as compared to IVA monotherapy. It can facilitate complete regression of polyps with higher odds.

Impact of the COVID-19 Pandemic on Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema in Japan.

Anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) improves visual acuity. However, repeated injections during routine outpatient visits are required to maintain this effect. The recent sudden global outbreak of coronavirus disease 2019 (COVID-19) had a major impact on daily life, including medical care, such as the provision of VEGF therapy. We retrospectively investigated the relationship between the number of anti-VEGF injections for DME and the number of new COVID-19-positive patients at 23 centers in Japan. We also surveyed ophthalmologists regarding the impact of the COVID-19 pandemic on anti-VEGF therapy. In the third and fourth waves of the pandemic, when the number of infected patients increased, the number of injections significantly decreased. In the first, third, and fourth waves, the number of injections increased significantly during the last month of each wave. Approximately 60.9% of ophthalmologists reported that the number of injections decreased after the pandemic. Of the facilities, 52.2% extended the clinic visit intervals; however, there was no significant difference in the actual number of injections given between before and after the pandemic. Although the number of injections temporarily decreased, Japanese ophthalmologists maintained the total annual number of anti-VEGF injections for DME during the pandemic.

Comparison of the regressive effects of aflibercept and brolucizumab on pigment epithelial detachment.

BACKGROUND: To compare the regressive effects of aflibercept and brolucizumab on pigment epithelial detachment (PED) in age-related macular degeneration. METHODS: Eighty-three eyes of 83 patients diagnosed with type 1 macular neovascularization were included and retrospectively analysed using multimodal imaging. Forty-nine eyes were treated with intravitreal aflibercept injections (IVA group), and 34 eyes were treated with brolucizumab (IVBr group), with three consecutive injections administered as induction therapy. Before treatment and 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group. RESULTS: In the IVA group, MH at baseline (228 ± 169 µm) diminished to 180 ± 150 (P = 0.2558), 165 ± 140 (P = 0.0962), and 150 ± 129 µm (P = 0.0284) at 1, 2, and 3 months after treatment, respectively; the reduction at 3 months was significant. In contrast, in the IVBr group, the MH was 307 ± 254 µm before treatment, and it decreased to 183 ± 156 µm (P = 0.0113), 139 ± 114 µm (P = 0.0003), and 125 ± 126 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively, and the reduction at 1 month was significant. In both groups, the MD did not regress significantly. CONCLUSIONS: The results suggested that the MH of PED after IVBr treatment regressed faster than that after IVA treatment.

Parasitomimetics: Can We Utilize Parasite-Derived Immunomodulatory Molecules for Interventions to Immunological Disorders?

Because our immune system has ability to expel microorganisms invading our body, parasites need evolution to maintain their symbiosis with the hosts. One such strategy of the parasites is to manipulate host immunity by producing immunomodulatory molecules and the ability of parasites to regulate host immunity has long been a target of research. Parasites can not only manipulate host immune response specific to them, but also influence the host's entire immune system. Such ability of the parasites may sometimes bring benefit to the hosts as many studies have indicated the "hygiene hypothesis" that a decreased opportunity of parasitic infections is associated with an increased incidence of allergy and autoimmune diseases. In other words, elucidating the mechanisms of parasites to regulate host immunity could be applied not only to resolution of parasitic infections but also to treatment of non-parasitic immunological disorders. In this review, we show how much progress has been made in the research on immunomodulation of host immunity by parasites. Here, we define the word 'parasitomimetics' as emulation of parasites' immunomodulatory systems to solve immunological problems in humans and discuss potential applications of parasite-derived molecules to other diseases.

Positioning of Bristol Stool Form Scale type 3 in constipation treatment satisfaction: A multicenter study in Japan.

BACKGROUND AND AIM: Many patients are not satisfied with chronic constipation (CC) treatments. The aim of this study was to identify factors linked to CC treatment satisfaction or dissatisfaction. METHODS: Our study population included patients who received CC treatment at a clinic or hospital. CC was diagnosed by a physician based on the patient's complaint. Treatment satisfaction was evaluated using the 28th question of the Patient Assessment of Constipation Quality of Life questionnaire. RESULTS: We conducted this study at 28 facilities. We included 167 patients (mean age 66.7 ± 15.2 years, male:female ratio is 1:3.07). Sixty-eight (40.7%) of patients were satisfied with their constipation treatment. Treatment dissatisfaction of CC was significantly associated with frequency of bowel movement <3/week (odds ratio [OR] = 0.376, 95% confidence interval [CI]: 0.156-0.904, P = 0.029) or Bristol Stool Form Scale (BSFS) type 3 (OR = 0.401, 95% CI: 0.170-0.946, P = 0.037). CONCLUSIONS: Our study showed that CC patients with BSFS type3 were not satisfied with constipation treatment. In general, BSFS types 3-5 are defined as normal stools. Therefore, BSFS type 3 may be set as a treatment goal even though the patient is not satisfied. The pathophysiology of CC differs by region and patient background. Therefore, parameters used to define successful treatment will be different by patient or region. We should reconsider the positioning of BSFS type 3 to improve treatment satisfaction for CC.

Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics.

Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.

Enumerated sparse extraction of important surgical planning features for mandibular reconstruction.

Because implicit medical knowledge and experience are used to perform medical treatment, such decisions must be clarified when systematizing surgical procedures. We propose an algorithm that extracts low-dimensional features that are important for determining the number of fibular segments in mandibular reconstruction using the enumeration of Lasso solutions (eLasso). To perform the multi-class classification, we extend the eLasso using an importance evaluation criterion that quantifies the contribution of the extracted features. Experiment results show that the extracted 7-dimensional feature set has the same estimation performance as the set using all 49-dimensional features.

Idiopathic Orbital Inflammation Appearing on the Affected Side of Preceding Myasthenia Gravis.

The patient was a 70-year-old man with idiopathic orbital inflammation (IOI) that appeared on the severely affected side of preceding myasthenia gravis (MG). The patient was diagnosed with MG 5 years prior to the onset of IOI. When IOI was diagnosed, an edrophonium test was negative. IOI was considered because he complained of left orbital pain, eyelid swelling, and cerebral MRI exhibited the enhanced lesions along the left orbital periosteum. A biopsy specimen revealed pathological findings compatible with IOI. The administration of corticosteroids was effective for improving the ocular symptoms. IOI should be considered when ocular symptoms deteriorated with soft tissue swelling/pain in MG patients.

2,3-Dihydroxybenzoate meta-Cleavage Pathway is Involved in o-Phthalate Utilization in Pseudomonas sp. strain PTH10.

Pseudomonas sp. strain PTH10 can utilize o-phthalate which is a key intermediate in the bacterial degradation of some polycyclic aromatic hydrocarbons. In this strain, o-phthalate is degraded to 2,3-dihydroxybenzoate and further metabolized via the 2,3-dihydroxybenzoate meta-cleavage pathway. Here, the opa genes which are involved in the o-phthalate catabolism were identified. Based on the enzymatic activity of the opa gene products, opaAaAbAcAd, opaB, opaC, and opaD were found to code for o-phthalate 2,3-dioxygenase, dihydrodiol dehydrogenase, 2,3-dihydroxybenzoate 3,4-dioxygenase, and 3-carboxy-2-hydroxymuconate-6-semialdehyde decarboxylase, respectively. Collectively, these enzymes are thought to catalyze the conversion of o-phthalate to 2-hydroxymuconate-6-semialdehyde. Deletion mutants of the above opa genes indicated that their products were required for the utilization of o-phthalate. Transcriptional analysis showed that the opa genes were organized in the same transcriptional unit. Quantitative analysis of opaAa, opaB, opaC, opaD, opaE, and opaN revealed that, except for opaB and opaC, all other genes were transcriptionally induced during growth on o-phthalate. The constitutive expression of opaB and opaC, and the transcriptional induction of opaD located downstream of opaB, suggest several possible internal promoters are existence in the opa cluster. Together, these results strongly suggest that the opa genes are involved in a novel o-phthalate catabolic pathway in strain PTH10.

Factors associated with poor therapeutic response in outpatients with irritable bowel syndrome: a multicenter study in Japan.

BACKGROUND: Some patients with irritable bowel syndrome (IBS) show poor response to treatment. However, risk factors associated with poor therapeutic response have not been determined. METHODS: This multicenter trial evaluated consecutive outpatients with IBS undergoing treatment for more than 1 month. Mental health status and physical function were evaluated using the Japanese version of the SF-8. Therapeutic response was evaluated using the IBS severity index-Japanese version (IBS-SIJ). Patients with IBS-SIJ scores ≥175 were defined as poor responders to treatment, whereas those with IBS-SIJ scores <175 were defined as good responders. The demographic and clinical characteristics of these two groups, along with medications, were compared. RESULTS: The study enrolled 131 participants, 75 with IBS-SIJ scores ≥175-56 with IBS-SIJ scores <175. Multiple logistic regression analysis showed that female sex [odds ratio (OR) 2.67, 95 % confidence interval (CI) 1.19-5.97, p = 0.0167] and mental component summary (MCS) of the SF-8 <40 (OR 2.58, 95 % CI 1.12-5.97, p = 0.0263) were independent risk factors for poor therapeutic response in patients with IBS. CONCLUSIONS: Lower MCS and female sex were risk factors for poor therapeutic response in patients with IBS. Ascertaining the mechanisms by which lower MCS and female sex are associated with poor therapeutic response in IBS may help design better treatments (Trial registration number: UMIN000016804).

New therapy using omega-3-Acid ethyl esters for decubitus ulcers and stasis dermatitis: a case report.

INTRODUCTION: In daily practice, it is common to experience difficulty in treating decubitus ulcers (pressure ulcers, also known as decubitus ulcers) and stasis dermatitis of the lower limbs. We hereby report that omega-3-acid ethyl esters were remarkably effective when administered to cases of refractory pressure ulcers and stasis dermatitis for the purpose of improving the blood flow and promoting blood circulation. CASE PRESENTATION: Case 1: A 21-year-old Japanese female with lower-body paralysis. Pressure ulcers appeared on the heel and first toe of her left lower extremity. Although the patient had been treated with various ointments such as dimethyl isopropylazulene and 0.9% iodine-containing ointment, the course showed no improvement, so omega-3-acid ethyl esters was administered orally, completely healing the ulcer of the first toe in 10 weeks. Case 2: A 76-year-old Japanese male. The patient had been treated on an outpatient basis for 15 years due to hypertension, heart failure, type 2 diabetes mellitus, and hyperlipidemia. Two years prior to this presentation, stasis dermatitis occurred in the lower limbs and at the end of last year, erosive ulcers appeared on the front part of the lower-right thigh and shin. Although treatment with various topical ointment and dressings was performed, the course showed no improvement. Oral administration of omega-3-acid ethyl esters was initiated. At 12 weeks, his condition entered the white phase and healed almost completely. CONCLUSIONS: This report is the first to document other treatment possibilities for pressure ulcer and/or stasis dermatitis in cases where the use of topical applied ointments and medications is difficult. This new therapy may therefore help physicians to treat pressure ulcers and stasis dermatitis.

Suspected idiopathic sclerosing orbital inflammation presenting as immunoglobulin G4-related disease: a case report.

INTRODUCTION: Idiopathic sclerosing orbital inflammation is a rare and ill-defined heterogeneous entity, and a distinct subset of orbital inflammation. Recently, attention has been focused on immunoglobulin G4-related disease complicated with fibrotic changes in some other organs with high serum immunoglobulin G4 levels. This report presents a case of suspected idiopathic sclerosing orbital inflammation complicated with high serum immunoglobulin G4 levels. CASE PRESENTATION: An 82-year-old Japanese woman had a 30-year history of chronic thyroiditis. She experienced right ptosis and eyelid swelling. These symptoms gradually developed over five years. The clinical and radiographic findings suggested that our patient had idiopathic sclerosing orbital inflammation. We were unable to obtain our patient's consent to perform a biopsy. While the serum immunoglobulin G level was within the normal limits, the serum immunoglobulin G4 level was significantly elevated. The serum immunoglobulin G4 levels decreased after the administration of oral prednisolone at a daily dose of 20 mg. In addition, the swelling and ptosis of the right upper eyelid disappeared gradually after four weeks. Our patient was then suspected to have idiopathic sclerosing orbital inflammation complicated with immunoglobulin G4-related disease and chronic thyroiditis. CONCLUSION: An orbital pseudotumor of this type is indicative of idiopathic sclerosing orbital inflammation immunoglobulin G4-related disease. Immunoglobulin G4 may thus be considered a subclass of immunoglobulin G when the serum immunoglobulin G level is within normal limits.

Effective therapy using voglibose for nonalcoholic steatohepatitis in a patient with insufficient dietary and exercise therapy: exploring other treatment possibilities.

A 56-year-old Japanese female with a 10-year history of thyroiditis presented to our institution. The laboratory data and clinical findings suggested that the patient had complicated nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (NASH) with autoimmune hepatitis according to the criteria by the application of the International Autoimmune Hepatitis score. The patient could not manage by herself so dietary- and exercise-based treatment was difficult. Accordingly, ursodeoxycholic acid and ezetimibe therapy was started and continued until the performance of a liver needle biopsy to define the diagnosis. However, no improvement in liver function was observed. In addition, pathological findings indicated that the patient had NASH. The patient was finally diagnosed as having NASH. Therefore, voglibose was added to the ursodeoxycholic acid and ezetimibe therapy, and this addition of voglibose actually took effect. The patient's serum aspartate transaminase and alanine aminotransferase levels decreased dramatically. This report is the first to document other treatment possibilities of NASH in a case when dietary therapy is difficult.

A new category for chronic sclerosing sialadenitis as an IgG4 related syndrome.

This report presents three cases of IgG4 related sclerosing disease complicated with chronic sclerosing sialadenitis. The clinical, radiographic and pathologic findings later suggested that the patients had chronic sclerosing sialadenitis. The submandibular gland tumour regressed in two patients. These patients were suspected to have Mikulicz's disease or Sjögren's syndrome, but the diagnostic criteria were not satisfied. The workup for chronic sclerosing sialadenitis revealed a significantly elevated value of serum IgG4. The patient was then diagnosed with IgG4 related sclerosing disease complicated with chronic sclerosing sialadenitis. After administering prednisolone to these patients, the serum IgG4 values decreased after 4 weeks. The current cases may represent a new category for Mikulicz's disease or Sjögren's syndrome as an IgG4 related sclerosing disease.

SAPHO syndrome with bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer.

The authors describe a case of SAPHO syndrome with bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer. The patient had undergone transurethral resection (TUR) and was treated with BCG immunotherapy following TUR. Two years after treatment for bladder cancer, the patient had palmoplantar pustulosis, and in the past 1 month suffered from pain localised to the anterior chest wall. The bone scintigraphy showed a strong focal enrichment in the right chest wall, suggesting spondyloarthropathy rather than malignant disease. On the basis of clinical and scintigraphy findings, SAPHO syndrome was diagnosed. The patient was treated with topical therapy and non-steroidal anti-inflammatory drugs and symptoms improved. The authors suggest that SAPHO syndrome might be caused by an association with BCG immunotherapy.