Diagnostic Accuracy of Point-of-Care Gram Stains in Obstructive Pyelonephritis due to Ureteral Stones.

Background: The diagnostic utility of point-of-care (POC) Gram stains for obstructive pyelonephritis with hydronephrosis is not well established. The current study aimed to assess the diagnostic accuracy of urine Gram stains in patients with obstructive pyelonephritis due to ureteral stones. Methods: A retrospective observational study was conducted on patients with obstructive pyelonephritis admitted to our hospital between January 2011 and December 2021. The diagnostic accuracy of Gram stains was evaluated based on the severity of hydronephrosis, including Gram stains performed by both trained physicians and microbiological technicians. Results: After analyzing 210 patients, POC Gram stains of bladder urine presented a sensitivity, specificity, positive predictive value, and negative predictive value of 86.8%, 81.8%, 93.7%, and 66.7%, respectively, for gram-negative rods and 65.7%, 83.4%, 48.9%, and 91.0%, respectively, for gram-positive cocci. The agreement between POC Gram stains and urine culture was good for gram-negative rods, with a kappa (κ) coefficient of 0.637 and agreement rate of 85.6%, and moderate for gram-positive cocci, with a κ coefficient of 0.435 and agreement rate of 80%. The agreement between POC Gram stains and bladder urine culture results for gram-negative rods was higher in the mild hydronephrosis group (κ coefficient = 0.677) than in the severe hydronephrosis group (κ coefficient = 0.466). Discrepancies in Gram stain results between physicians and technicians were observed in 21 of 180 cases (11.7%). Conclusions: POC Gram stains for gram-negative rods may be a useful diagnostic tool for obstructive pyelonephritis, particularly in cases of mild hydronephrosis.

Skin care by washing with water is not inferior to washing with a cleanser in children with atopic dermatitis in remission in summer: WASH study.

BACKGROUND: Washing with water is not inferior to washing with soaps and detergents in children with atopic dermatitis (AD) in remission during the fall-winter seasons. We investigated whether this finding varies during summer based on the type of cleanser (soaps and detergents). METHODS: This evaluator-blinded, pragmatic, randomized, and non-inferiority study enrolled patients with AD whose eczema was controlled following regular steroid ointment application 2 days/week. For 8 ± 4 weeks, participants washed their upper and lower limbs with a cleanser on one side and with water alone on the other. Each participant chose either a weakly alkaline soap or an acidic detergent. The primary outcome was the Eczema Area and Severity Index (EASI) score at week 8 ± 4. RESULTS: The data of 43 of the 47 registered participants were analyzed. The median patient age was 44 (23-99) months; 28 and 15 participants chose weakly alkaline and acidic cleansers, respectively. At week 8 ± 4, EASI scores of the water and cleanser sides were 0.00 (0.00-0.40) and 0.15 (0.00-0.40), respectively (p = 0.74). The difference between both sides was 0.00 (-0.07 to 0.14); the limits of the 95 % confidence interval did not reach the pre-specified non-inferiority margin. No difference was observed in the median Patient-Oriented Eczema Measure score, number of additional steroid ointment applications, and occurrences of skin infections. There were no differences between the cleanser types in any of the results. CONCLUSIONS: We demonstrated that washing with water was not inferior to that with a cleanser in patients with AD in the maintenance phase during summer, regardless of the type of cleanser.

Wernicke encephalopathy: limitations in a laboratory and radiological diagnosis.

Wernicke encephalopathy is an emergent neurological disorder caused by vitamin B1 (thiamine) deficiency. Here, we present a case of Wernicke encephalopathy in a male patient in his 70s with normal serum thiamine levels and MRI findings on admission. He had a history of heavy alcohol consumption and a gradual decrease in food intake. On arrival at the hospital, his consciousness was impaired which persisted even after glucose replacement. Moreover, horizontal nystagmus and cerebellar ataxia were observed. Head CT scan and MRI revealed no abnormal findings. Further, his serum thiamine level was within the normal range. The patient was clinically diagnosed with Wernicke encephalopathy, and high-dose thiamine therapy was started. Then, his symptoms improved immediately. Thus, in case of clinical suspicion, treatment for Wernicke encephalopathy must be initiated promptly even in patients with normal serum thiamine levels.

Skin and soft tissue infections and bacteremia caused by Vibrio cincinnatiensis.

Vibrio cincinnatiensis is a halophilic species found in marine and estuarine environments worldwide. It is a rare pathogen whose impact on humans has remained unclear; only two cases of V. cincinnatiensis infection have been reported in humans, so far. A 63-year-old man with a history of myocardial infarction and type 2 diabetes mellitus presented to the emergency department with fever and dyspnea. Physical examination demonstrated notable abdominal distension and bilateral lower leg edema. marked abdominal distension and bilateral lower leg edema. The patient was diagnosed with bacteremia and exacerbated heart failure. Blood and skin cultures revealed the presence of the gram-negative pathogen V. cincinnatiensis. Combined antibiotic therapy using intravenous tazobactam /piperacillin resulted in a gradual recovery with no recurrence observed at the 9-month follow-up. To the best of our knowledge, this is the third case of V. cincinnatiensis infection reported in humans and the first one to be associated with skin and soft tissue infection. We suggest that although V. cincinnatiensis is a rare pathogen, it should be considered as a potential infective agent in the differential diagnosis of immunocompromised patients, regardless of any recent exposure to seawater or marine products.

Paediatric progressive primary tuberculosis.

A previously healthy 13-year-old Japanese girl with a BCG vaccination history and no tuberculosis (TB) exposure history presented to the hospital with mild dyspnea for 1 month and fever for 5 days. Computed tomography showed consolidation with a pleural effusion, obstructed left main bronchus with an air bronchogram, and traction bronchiectasis of the left upper lobe (Fig. 1A, B). No improvement was observed with ampicillin. Computed tomography on day 23 showed a new granular shadow in the right upper lobe (Fig. 1C). Despite a negative interferon-gamma release assay (IGRA) result, the sputum on day 55 was positive for acid-fast bacilli on a ZiehlNeelsen stain and Mycobacterium tuberculosis on polymerase chain reaction. A fourdrug antituberculous regimen was initiated and she recovered rapidly. TB exposure history, positive tuberculin skin test or IGRA, and typical imaging findings are the triad for primary TB diagnosis (Perez-Velez and Marais, 2012; Lewinsohn et al., 2017; Ahmed et al., 2020). In pediatric primary TB, consolidation may be present and can be misdiagnosed as bacterial pneumonia; however, massive consolidation is rare (GriffithRichards et al., 2007). Primary pulmonary TB should be considered in children with lung consolidation that is unresponsive to antibiotics, despite negative IGRA and TB exposure history.

Efficacy and safety of propranolol cream in infantile hemangioma: A prospective pilot study.

Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35-150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1-85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.

Acute Dacryoadenitis due to Primary Epstein-Barr Virus Infection.

We herein present the case of a 28-year-old male patient who presented with fever and bilateral upper eyelid edema without other upper airway symptoms and was diagnosed with acute dacryoadenitis due to Epstein-Barr virus (EBV) infection. The patient's medical history was unremarkable. Laboratory tests revealed lymphocytosis with atypical lymphocytes and abnormal liver function tests. Physical examination and computed tomography revealed swelling in the lacrimal glands, and serological tests confirmed EBV infection. Although rare, ocular symptoms of primary EBV infection are important for diagnosis. Acute dacryoadenitis should be considered as a rare manifestation and an underdiagnosed complication of primary EBV infection.

Predictors of initial oral food challenge outcome in food protein-induced enterocolitis syndrome.

Background: There is a paucity of data on predictors of clinical history in oral food challenge (OFC) outcome for the initial diagnosis of food protein-induced enterocolitis syndrome (FPIES). Objective: This study aimed to identify predictors for the diagnosis of FPIES. Methods: The study included patients who underwent OFC to diagnose FPIES from 2010 to 2021. Patients with a positive OFC result were classified as belonging to the FPIES group, and those with negative OFC result within 120 days from the last symptomatic episode were classified as belonging to the no-allergy (NA) group. Background factors were analyzed in the groups. Results: A total of 50 OFCs to 12 different foods were conducted in 50 patients. Of those 50 patients, 30 were classified as belonging to the FPIES group. No significant difference was observed between the FPIES and NA groups with respect to background factors, including the features of symptomatic episodes and examinations of immediate-type allergy. A history of asymptomatic ingestion was observed in 23 of 24 and 13 of 19 patients in the FPIES and NA groups, respectively; thus, it was significantly more common in patients with FPIES. The diagnostic rate of patients with fewer than 3 symptomatic episodes was 52%, and that of patients with 3 episodes or more was 75%, not considering a patient without available data. Conclusions: A definite diagnosis of FPIES should be based on OFC, as there are no predictors for OFC positivity other than a history of asymptomatic ingestion. The absence of asymptomatic ingestion history was a negative predictor for the diagnosis of FPIES.

Subtypes of atopic dermatitis: From phenotype to endotype.

Atopic dermatitis (AD) is a heterogenous disorder and can be classified into different types. Stratification of subtypes may enable personalized medicine approaches. AD can be categorized into the IgE-high, extrinsic subtype and the IgE-normal, intrinsic subtype. While extrinsic AD is the major subtype possessing skin barrier impairment (high incidence of filaggrin mutations), intrinsic AD occupies about 20% of AD with female dominance and preserved barrier. Extrinsic AD exhibits protein allergy and food allergy, but intrinsic AD shows metal allergy possibly in association with suprabasin deficiency. In particular, accumulated knowledge of food allergy has more clearly characterized extrinsic AD. European American (EA) and Asian AD subtypes have been also proposed. Asian patients with AD are characterized by a unique blended immune dysregulation and barrier feature phenotype between EA patients with AD and those with psoriasis. In another ethnic study, filaggrin loss-of-function mutations are not prevalent in African American patients with AD, and Th1/Th17 attenuation and Th2/Th22 skewing were seen in these patients. Recent endotype classification provides new insights for AD and other allergic disorders. Endotype is defined as the molecular mechanisms underlying the visible features/phenotype. Endotype repertoire harbors activation of type 2 cytokines, type 1 cytokines, and IL-17/IL-22, impairment of epidermal barrier, and abnormalities of intercellular lipids. Classification of endotype has been attempted with serum markers. These lines of evidence indicate a need for personalized or precision medicine appropriate for each subtype of AD.

Questionnaire Survey of Possible Association of Allergic Diseases with Adverse Reactions to SARS-CoV-2 Vaccination.

To protect against COVID-19, SARS-CoV-2 vaccines have been widely used. Besides anaphylaxis, some less severe adverse effects may occur at higher frequencies. It remains unclear whether present or past histories of allergic diseases exert effects on local and systemic reactions. We conducted a questionnaire survey among workers in our hospital. We analyzed the adverse effects occurring after the first and second doses of the Pfizer-BioNTech vaccine in 955 subjects. The presence or absence of local injection reactions and systemic reactions (headache, fatigability, fever, muscle pain, and joint pain) was questioned. The intensities of these reactions were graded on a scale of 0-4 (except fever) or 0-2 (fever). The allergic diseases that we focused on were bronchial asthma, atopic dermatitis, food allergy, pollinosis, and hand eczema. For the systemic reactions, fatigability after the first dose tended to be more severe in the bronchial asthma than in the non-allergic group. Headache, joint pain, and fever tended to be more severe in the food allergy than in the non-allergic group after the second dose. For the local skin reactions, atopic dermatitis subjects tended to show rather less severe local skin reactions after the second dose. The results contribute to the guidelines for the care of individuals with different allergy histories, so that they may safely receive their vaccine.

Photobacterium damselae subsp. damselae bacteraemia in a patient with liver cirrhosis.

Photobacterium damselae subsp. damselae is a family of Vibrionaceae and exists in the marine environment. The organism rarely causes soft-tissue infection in humans; moreover, most of the infected individuals have a history of fishing or exposure to brackish water. We experienced the case of a 63-year-old patient with a history of liver cirrhosis (Child-Pugh class B) who presented with a fever and swelling of the left leg with pain. His symptoms developed after fishing and eating raw fish with exposure of brackish water. He was diagnosed with cellulitis, and Photobacterium damselae spp. damselae was detected in blood culture. The patient was treated with ceftazidime and minocycline and he was discharged after recovery. We need to be aware that in immunocompromised patients with cellulitis exposed to brackish water, organisms other than Staphylococci and Streptococci may be the causative organisms.

Empyema associated with a cough-induced rib fracture.

A 44-year-old man presented to the emergency department with fever and right anterior chest pain. He reported a persistent cough and the development of sudden-onset right anterior chest pain after coughing. The inspiratory pain in the right lung was severe, and therefore deep breathing was impossible. Chest CT revealed a fracture in the right seventh rib with consolidation and pleural effusion. A pleural fluid culture test result was positive for methicillin-susceptible Staphylococcus aureus He was diagnosed with empyema associated with a cough-induced rib fracture. Thoracic drainage tube placement and intravenous antibiotic therapy successfully ameliorated his condition. He was discharged on day 13 and switched to an 8-week course of oral antibiotic therapy. There was no clinical relapse at the 6-month follow-up.

Phosphorylated proteome analysis of a novel germline ABL1 mutation causing an autosomal dominant syndrome with ventricular septal defect.

BACKGROUND: A gain-of-function mutation in germline ABL1 causes a syndrome including congenital heart defects. However, the molecular mechanisms of this syndrome remain unknown. In this study, we found a novel ABL1 mutation in a Japanese family with ventricular septal defect, finger contracture, skin abnormalities and failure to thrive, and the molecular mechanisms of these phenotypes were investigated. METHODS AND RESULTS: Whole-exome sequencing on several family members revealed a novel mutation (c.1522A > C, p.I508L) in the tyrosine kinase domain of ABL1, and complete co-segregation with clinical presentations was confirmed in all members. Wild-type and mutant ABL1 were transfected into human embryonic kidney 293 cells for functional analysis. Western blotting confirmed that tyrosine phosphorylation in STAT5, a substrate of ABL1, was enhanced, and the novel mutation was proved to be a gain-of-function mutation. Since this novel mutation in ABL1 enhances tyrosine kinase activity, phosphorylated proteome analysis was used to elucidate the molecular pathology. The proteome analysis showed that phosphorylation in proteins such as UFD1, AXIN1, ATRX, which may be involved in the phenotypes, was enhanced in the mutant group. CONCLUSIONS: The onset of congenital heart defects associated with this syndrome appears to involve a mechanism caused by UFD1 common to 22q.11.2 deletion syndrome. On the other hand, AXIN1 and ATRX may be important in elucidating the mechanisms of other phenotypes, such as finger contracture and failure to thrive. Verification of these hypotheses would lead to further understanding of the pathophysiology and the development of treatment methods.

Comprehensive pathogen detection in sera of Kawasaki disease patients by high-throughput sequencing: a retrospective exploratory study.

BACKGROUND: Kawasaki disease (KD) is an idiopathic systemic vasculitis that predominantly damages coronary arteries in children. Various pathogens have been investigated as triggers for KD, but no definitive causative pathogen has been determined. As KD is diagnosed by symptoms, several days are needed for diagnosis. Therefore, at the time of diagnosis of KD, the pathogen of the trigger may already be diminished. The aim of this study was to explore comprehensive pathogens in the sera at the acute stage of KD using high-throughput sequencing (HTS). METHODS: Sera of 12 patients at an extremely early stage of KD and 12 controls were investigated. DNA and RNA sequences were read separately using HTS. Sequence data were imported into the home-brew meta-genomic analysis pipeline, PATHDET, to identify the pathogen sequences. RESULTS: No RNA virus reads were detected in any KD case except for that of equine infectious anemia, which is known as a contaminant of commercial reverse transcriptase. Concerning DNA viruses, human herpesvirus 6B (HHV-6B, two cases) and Anelloviridae (eight cases) were detected among KD cases as well as controls. Multiple bacterial reads were obtained from KD and controls. Bacteria of the genera Acinetobacter, Pseudomonas, Delfita, Roseomonas, and Rhodocyclaceae appeared to be more common in KD sera than in the controls. CONCLUSION: No single pathogen was identified in serum samples of patients at the acute phase of KD. With multiple bacteria detected in the serum samples, it is difficult to exclude the possibility of contamination; however, it is possible that these bacteria might stimulate the immune system and induce KD.