Identification and characterization of a novel α-haemolytic streptococci, Streptococcus parapneumoniae sp. nov., which caused bacteremia with pyelonephritis.

OBJECTIVES: We report a case of bacteremia with pyelonephritis in an adult male with an underlying disease caused by α-hemolytic streptococci. α-Hemolytic streptococci were isolated from blood, but it was challenging to identify its species. This study aimed to characterize the causative bacterium SP4011 and to elucidate its species. METHODS: The whole-genome sequence and biochemical characteristics of SP4011 were determined. Based on the genome sequence, phylogenetic analysis was performed with standard strains of each species of α-hemolytic streptococci. Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values were calculated. RESULTS: SP4011 showed optochin susceptibility and bile solubility, but did not react with pneumococcal omni antiserum. Phylogenetic analysis of the whole-genome sequence showed that SP4011 clustered with S. pneumoniae and S. pseodopneumoniae and was most closely related to S. pseodopneumoniae. Genomic analysis revealed that ANI and dDDH values between SP4011 and S. pseodopneumoniae were 94.0 % and 56.0 %, respectively, and between SP4011 and S. pneumoniae were 93.3 % and 52.2 %, respectively. Biochemical characteristics also showed differences between SP4011 and S. pseodopneumoniae and between SP4011 and S. pneumoniae. These results indicate that SP4011 is a novel species. CONCLUSION: Our findings indicate that SP4011 is a novel species of the genus Streptococcus. SP4011 has biochemical characteristics similar to S. pneumoniae, making it challenging to differentiate and requiring careful clinical diagnosis. This isolate was proposed to be a novel species, Streptococcus parapneumoniae sp. nov. The strain type is SP4011T (= JCM 36068T = KCTC 21228T).

Blood perfusion with polymyxin B immobilized columns in patients with COVID-19 requiring oxygen therapy.

Extracorporeal blood purification with polymyxin B immobilized fiber column direct hemoperfusion (PMX-DHP), is reported to be effective in treating COVID-19 pneumonitis with oxygen demand. This multicenter prospective study evaluated the efficacy and safety of PMX-DHP in oxygen-requiring patients with COVID-19 admitted between September 28, 2020, and March 31, 2022. The primary endpoint was the percentage of clinical improvement 15 days after treatment. The secondary endpoint was the percentage of worsened disease status. Data from the COVID-19 patient registry were used for the synthetic control group. The improvement rate on Day 15 did not differ between PMX-treated patients and controls; however, the deterioration rate was 0.38 times lower in the PMX-treated group, and the death rates on Day 29 were 0 and 11.1% in the PMX-treated and control groups, respectively. The PMX group showed a 0.73 times higher likelihood for reduced intensive care demand, as 16.7% of PMX-treated patients and 22.8% of controls worsened. After treatment blood oxygenation improved, urinary ß2-microglobulin and liver-type fatty acid-binding protein showed significant decreases, and IL-6 decreased once during treatment but did not persist. In this study, PMX treatment effectively prevented the worsening of COVID-19 pathology, accompanied by improved oxygenation. PMX treatment to remove activated cells may effectively improve patient outcomes.

Urinary liver-type fatty acid-binding protein level as a prognostic indicator of acute kidney injury secondary to severe falciparum malaria.

Acute kidney injury (AKI) secondary to severe falciparum malaria possesses a high mortality rate; however, a prognostic marker of renal dysfunction has not yet been identified. Thus, we reported a case of a patient with AKI secondary to falciparum malaria who underwent hemodialysis and a renal biopsy due to prolonged renal dysfunction. The male patient, in his 50 s, presented to our hospital with vomiting, diarrhea, fever, and decreased level of consciousness. The Giemsa-stained peripheral blood film revealed approximately 5% parasitemia, and a rapid diagnostic test was positive for Plasmodium falciparum. He was diagnosed with severe falciparum malaria and was started on quinine hydrochloride. Hemodialysis was initiated due to the decreased urine output and fluid retention. Subsequently, he was weaned off hemodialysis. The histopathological analysis of a renal biopsy revealed interstitial fibrosis, tubular atrophy, and chronic inflammatory cell infiltration; thus, malarial nephropathy was diagnosed. Thereafter, his renal function stabilized, and he was discharged from the hospital. The urinary liver-type fatty acid-binding protein (L-FABP) level decreased before renal function improved. Our report highlighted that long-term follow-up is essential for severe AKI secondary to malaria. The urinary L-FABP level may be a useful prognostic indicator of AKI secondary to severe falciparum malaria.

A retrospective study describing the effective exchange of total blood plasma for disease control in the exacerbation of serpiginous choroiditis.

INTRODUCTION: Serpiginous choroiditis presents with large yellow-white exudative lesions that occur near the optic nerve papillae, that progresses slowly with repeated relapses and cures. Although infection and autoimmunity have been implicated, the cause is unknown. METHODS: A man was diagnosed with serpiginous choroiditis on clinical and other examinations. He started treatment with oral corticosteroids, cyclophosphamide, adalimumab, azathioprine, rituximab, and mycophenolate mofetil. Only the steroids and cyclophosphamide had a therapeutic effect. Plasma exchange was initiated, and the lesions quickly resolved. RESULTS: Disease control has been maintained by plasma exchange and cyclophosphamide during flare-ups in the fall and winter, suggesting that plasma exchange is effective in the treatment of serpiginous choroiditis. CONCLUSION: The reproducible response with each recurrence suggests a strong association between the disease and autoimmunity. Furthermore, that some, as yet unknown, autoantibodies are involved in the pathogenesis of serpiginous choroiditis.

A case of rapidly progressive glomerulonephritis with double-positive anti-GBM antibody and MPO-ANCA after SARS-CoV-2 vaccination and relapse during 1 year follow-up.

Although mRNA vaccines for COVID-19 are highly beneficial and are recommended for patients with kidney disease, adverse reactions in some patients after vaccination have been problematic. Various vasculitis and renal disorders have been reported after vaccination; however, a causal relationship has not yet been identified. In this report, we describe a case of rapidly progressive glomerulonephritis that developed after SARS-CoV-2 vaccination, in which both anti-glomerular basement membrane (anti-GBM) and myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) were present. The patient's renal biopsy showed that of the 48 glomeruli in total, four showed global sclerosis and none showed segmental sclerosis. The biopsy showed 11 cellular glomerular crescents and 5 fibrocellular glomerular crescents. Renal function improved with steroids, rituximab, and plasma exchange. Approximately 9 months later, MPO-ANCA was again elevated, and the pulmonary lesions worsened, again requiring multidisciplinary treatment. This case suggests that caution should be exercised in the development of double-positive disease after vaccination, and that long-term observation may be necessary because of the possibility of relapse.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases.

Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES: To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN: Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS: Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS: Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE: Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

Usefulness of gallium-67 scintigraphy for evaluating the histopathological activity in interstitial nephritis.

BACKGROUND: Interstitial nephritis is a common cause of renal failure. Gallium-67 scintigraphy is reportedly useful for diagnosing interstitial nephritis; however, its ability to assess disease activity remains unknown. We aimed to analyze the relationship between the renal uptake of gallium-67 and the disease activity in interstitial nephritis. METHODS: We retrospectively analyzed the data of patients who underwent gallium-67 scintigraphy at a hospital in Tokyo. The renal uptake adjusted for the soft tissues beneath the kidneys was semi-quantitatively evaluated. We compared the renal uptake levels between patients clinically diagnosed with and without interstitial nephritis. Among those undergoing renal biopsy, we evaluated the predictive ability of gallium-67 scintigraphy and analyzed the renal uptake levels regarding the disease activity through a histopathological analysis. RESULTS: We included 143 patients; among them, 30, 17, and 96 patients were clinically diagnosed with interstitial nephritis, other kidney diseases, and non-kidney diseases, respectively. The renal uptake of gallium-67 was the highest among patients with interstitial nephritis. Among the 25 patients who underwent renal biopsy, 15 were pathologically diagnosed with interstitial nephritis. The renal uptake levels showed a high discriminative ability (C-statistic: 0.83). Furthermore, net reclassification improvement with the addition of gallium-67 scintigraphy to N-acetyl-ß-D-glucosaminidase for the prediction of interstitial nephritis was 1.14. Histopathological analysis revealed a positive correlation between renal uptake and inflammation in the cortex and peritubular capillaries. CONCLUSIONS: This study confirmed the diagnostic value and potential usefulness of gallium-67 scintigraphy for evaluating interstitial nephritis.

Adjuvant diagnosis of tuberculosis in hemodialysis patients using fourth generation interferon γ releasing assay.

INTRODUCTION: Dialysis patients have a 10-25 times higher risk of reactivation of tuberculosis (TB). In this study, we investigated the diagnostic ability of QuantiFERON (QFT)-plus for TB in hemodialysis patients. QFT-plus, an interferon gamma release assay, is characterized by its use of CD4 and CD8 T cell signals. METHODS: Hemodialysis patients aged 20 years or older who underwent QFT-plus measurement in our hospital were included, inclusion criteria being fever above 37°C, high inflammatory response, and infiltrative pulmonary shadows. RESULTS: Forty-six patients were enrolled. Of these, 15% were QFT positive, 4% were diagnosed with active TB, 76% were QFT negative, 8% had inconclusive results. Sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 87.5%, 28%, and 100%, respectively. CONCLUSIONS: QFT-plus may be useful for the diagnosis of active TB in dialysis patients. Further studies in cohorts with larger sample sizes are expected.

Safety of casirivimab/imdevimab administration in a SARS-CoV-2 positive maintenance dialysis patient in Japan.

Controlling excessive cytokine secretion is a crucial therapeutic strategy for managing coronavirus disease 2019 (COVID-19). Patients on dialysis are at a high risk of severe disease, given abnormal immune responses that can lead to prolonged inflammation. Moreover, patients undergoing dialysis have limited treatment options, as neither remdesivir nor baricitinib is available. The novel neutralizing monoclonal antibody cocktail REGEN-COV (formerly known as REGN-COV2; casirivimab/imdevimab), recently approved in Japan, is a promising drug for preventing severe diseases. However, there are few reports regarding its use in patients undergoing dialysis in Japan. Herein, we report the safe use of antibody cocktail therapy in patients with COVID-19 on hemodialysis receiving maintenance dialysis in Japan. Infusion reactions were not observed during administration. Due to the increasing number of patients with COVID-19 and the limited capacity of the healthcare system, antibody cocktail therapy needs to be enhanced. Antibody cocktail therapy for severe diseases can be safely administered to patients undergoing dialysis who do not require supplemental oxygen.

Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits without Conspicuous Mesangial Proliferation, Complicated with Squamous Cell Lung Carcinoma.

We performed a renal biopsy for nephrotic syndrome in a patient with squamous cell lung carcinoma, which can worsen the prognosis. Chemoradiation therapy was effective for the cancer and proteinuria; we thus inferred that the nephrotic syndrome had been closely associated with the carcinoma. A pathological analysis of the kidney showed monoclonality for λ chain, satisfying the diagnostic criteria of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID); however, conspicuous mesangial proliferation was not observed. This is the first case of PGNMID complicated with lung carcinoma; furthermore, our findings underscore the importance of examining renal lesions and assessing monoclonality in cancer patients.

IL-6-producing Renal Cell Carcinoma Causing Renal and Endocrine Paraneoplastic Syndromes.

An 83-year-old man with stable chronic kidney disease (CKD) exhibited a sudden increase in urinary N-acetyl-ß-D-glucosaminidase and protein excretion, suggesting aggravated kidney damage. Simultaneously, he lost diabetic control, requiring up to 54 units of insulin daily. A detailed examination revealed the presence of renal cell carcinoma, which was surgically resected and confirmed to be interleukin-6-positive by immunohistochemistry. Postoperatively, his uni-nephrectomy necessitated hemodialysis, but the patient's insulin resistance was ameliorated; no medication was required to control diabetes, suggesting that the tumor had caused the insulin resistance. This report describes a case of a tumor secreting interleukin-6, which affects both the control of diabetes and CKD progression.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

The HTML version of this Article contained errors in Supplementary Figure S2 "Flowchart of the lyso-Gb3 screening and gene analysis in female patients", which have been detailed in the associated Correction.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

PURPOSE: Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females. METHODS: Between 1 July 2014 and 31 December 2015, we screened 2,359 patients (1,324 males) referred from 168 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively. RESULTS: Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml-1) and low α-Gal A activity (≤4.0 nmol h-1 ml-1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 14 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance). CONCLUSION: Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

In the above article, we noticed that one female patient in the positive group (plasma lyso-Gb3 7.6 ng/ml, α-galactosidase A activity 4.9 nmol/h/ml) who presented at the neurology clinic was already diagnosed with Fabry disease before the current study. We excluded patients with a confirmed diagnosis of Fabry disease and those with relatives known to have Fabry disease. To accurately describe the information in the current study, we must exclude this patient from the analysis. We have accurately revised this information as follows.

Atypical cause of intractable diarrhea in a hemodialysis patient, masked by Clostridium difficile-associated diarrhea and ischemic colitis: a case report.

BACKGROUND: Patients with end-stage kidney disease (ESKD) most commonly complain of gastrointestinal symptoms, such as diarrhea. Diarrhea negatively affects patient quality of life and has miscellaneous etiologies, such as Clostridium difficile-associated diarrhea (CDAD) and ischemic colitis. However, it is sometimes extremely difficult to determine the true etiology given the comorbidities and complications the patients have. A rare cause of diarrhea is ulcerative colitis (UC), which commonly affects the rectum and proximal colon in a continuous fashion. UC with rectal sparing or segmental distribution, although atypical, sometimes leads to misdiagnosis. Herein, we present a case of UC in a patient on hemodialysis with intractable diarrhea; we initially considered that the diarrhea was caused by CDAD and ischemic colitis. CASE PRESENTATION: A 69-year-old man with a history of hypertension, bilateral thalamic hemorrhage, and decreased kidney function was admitted to our hospital because of congestive heart failure. Volume control was impossible due to renal dysfunction and he was started on hemodialysis. Thereafter, he received various antibiotics for bacterial infections. Simultaneously, he experienced continuous watery, and sometimes bloody, diarrhea, which was diagnosed as CDAD owing to a positive stool test for Clostridium difficile toxins. Antibiotic treatment for CDAD did not result in symptom relief. Subsequently, we performed colon biopsy via colonoscopy, and the pathology showed virtually no inflammation with rectal sparing and segmental distributions. These findings favored the presence of ischemic colitis due to arteriosclerosis and ESKD rather than infections. He died of cardiac arrest before the diarrhea was alleviated. Finally, UC was revealed on autopsy as the main cause of the uncontrollable diarrhea. CONCLUSIONS: Patients with ESKD have a greater risk of developing CDAD and ischemic colitis, which have clinical features that sometimes overlap with those of UC, as in the present case. This case emphasizes the importance of correctly diagnosing the etiology of intractable diarrhea and the fact that other diarrhea etiologies can obscure the existence of inflammatory bowel disease, which should be considered and treated properly when patients on hemodialysis present with intractable diarrhea.

Evaluating the Efficacy of Double-Filtration Plasmapheresis in Treating Five Patients With Drug-Resistant Pemphigus.

Double-filtration plasmapheresis is an effective and safe treatment for pemphigus. We retrospectively evaluated the decrease in autoantibody titer and pemphigus disease area index following double-filtration plasmapheresis in five patients with moderate to severe pemphigus, who were physically and/or serologically unresponsive to 1.0 mg/kg per day of prednisolone and other supportive drugs and ointments. The percentage reduction in autoantibodies 85.6 ± 14.4% (P = 0.00014), and that in pemphigus disease area index was 75.4 ± 24.3% (P = 0.0023). No side-effects were observed. All patients exhibited clinical improvement after undergoing double-filtration plasmapheresis, and the prednisolone dose was reduced by 41 ± 8.9 mg (P = 0.0005) approximately 3 months after double-filtration plasmapheresis. To our knowledge, this is the first report evaluating the efficacy of double-filtration plasmapheresis with pemphigus disease area index, and it demonstrated that double-filtration plasmapheresis is a safe "subtracting" treatment for patients with drug-resistant pemphigus.

Vascular adhesion protein-1 enhances neutrophil infiltration by generation of hydrogen peroxide in renal ischemia/reperfusion injury.

Vascular adhesion protein-1 (VAP-1) is a unique molecule since it acts as an adhesion molecule as well as an ectoenzyme catalyzing oxidative deamination of primary amines and generates hydrogen peroxide in the extracellular space. While VAP-1 is implicated in various inflammatory diseases, its role in acute kidney injury is less characterized. Here we studied VAP-1 expression in the kidney and the effect of its inhibition in a rat model of renal ischemia/reperfusion injury. VAP-1 was predominantly expressed in pericytes, which released enzymatically active enzyme. In vivo, a specific VAP-1 inhibitor, RTU-1096, significantly ameliorated rat renal ischemia/reperfusion injury and decreased neutrophil infiltration measured 12 hours after injury without altering macrophage or T lymphocyte populations. The protective effect of VAP-1 inhibition was lost in neutrophil-depleted rats, suggesting its inhibition ameliorated renal ischemia/reperfusion injury by suppressing neutrophil infiltration. To investigate whether hydrogen peroxide generated by VAP-1 enzyme reaction enhances neutrophil infiltration, we conducted an under-agarose migration assay with purified human neutrophils. Recombinant human VAP-1 significantly induced neutrophil migration, which was almost completely inhibited by RTU-1096 or catalase. Thus, VAP-1 plays a critical role in the pathophysiology of renal ischemia/reperfusion injury by enhancement of neutrophil infiltration generating a local hydrogen peroxide gradient. Hence, VAP-1 inhibition may be a novel therapy in ischemic acute kidney injury.