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Cefazolin sodium is a first-generation cephalosporin antibiotic and has been used worldwide since the early 1970s. It is used for the treatment of bacterial infections in various organs, such as the respiratory tract, skin and skin structure, genital tract, urinary tract, biliary tract, and bone and joint infections. It has also been used for septicemia due to susceptible gram-positive cocci (except Enterococcus), some gram-negative bacilli including E. coli, Proteus, and Klebsiella may be susceptible, and for perioperative prophylaxis. After the introduction of penicillins and other cephalosporins, occasional outbreaks of methicillin-resistant Staphylococcus aureus were noted. As a result, vancomycin use was increased; however, very recently and most alarmingly, vancomycin-resistant strains have been described. In this setting, to avoid the risk of the development of vancomycin-resistant strains further, vancomycin use should be curtailed. In consideration of this historical background, the appropriate use of antibiotics, such as dosage, dosage intervals, and the duration of administration is required not only for the protection of patients' health but also for the prevention of the development of drug resistance. Cefazolin has been used in clinical practice for about 40 years, and a large body of evidence has been accumulated, and its efficacy and safety are well established compared with other antibiotics. Therefore, cefazolin has been chosen as a first-line anti-microbial for prophylaxis after various surgical procedures, including cardiovascular surgery, hysterectomy, arthroplasty and so on. Based on these facts, especially for the prophylaxis of surgical site infections, the first-generation cephalosporin, cefazolin, is now being "re-visited". [ABSTRACT FROM AUTHOR]

The concentration of C2 was determined by electroimmunoassay in sera from healthy controls, patients with systemic lupus erythematosus (SLE), their relatives and patients with other diseases. Monospecific anti-human C2 serum was obtained by immunizing rabbits with purified human C2 and then absorbing the rabbit serum with inactivated normal human serum that was made insoluble. In addition, it was shown that human C2 could be purified by means of affinity chromatography on anti-C2 antibody coupled Sepharose. The serum concentration of C2 was 37.8 ± 5.0 (s.d.) μg/ml in healthy controls (n = 133). In patients with SLE, the values were below normal in the active phase and were within normal limits in the inactive phase, showing good correlations with other complement parameters such as CH50, C4, C3 and factor B. C2 concentration was well correlated with C2 haemolytic activity in the inactive phase of SLE, but there was no relationship between the two in the active phase. The mean value of C2 concentration in the relatives of patients with SLE showed no significant difference from that in healthy controls. C2 concentration tended to be high in patients with scleroderma, polymyositis, rheumatoid arthritis, Behçet's disease and aortitis syndrome. However, the values were often low in patients with chronic liver diseases, suggesting a decrease of C2 production in the liver. [ABSTRACT FROM AUTHOR]

The hepatic involvement of 57 patients with systemic lupus erythematosus (SLE) was studied with special reference to liver membrane autoantibody (LMA). Liver abnormalities were found predominantly in patients with active SLE (27/48 (56%) in active SLE v 3/20 (15%) in inactive SLE). They were, however, rather mild or moderate and tended to disappear as the disease activity of SLE decreased. In this respect the liver abnormalities observed in this study differed from those in patients with lupoid hepatitis. The incidence of LMA in active SLE (8/11 (73%] was significantly greater than that in inactive SLE (4/12 (33%)). The mean LMA index value in active SLE was 8.3, which was also greater than the 2.9 in inactive SLE. Furthermore, in active SLE the mean LMA titre was significantly higher in patients with liver abnormalities than in those without. These results suggest that LMA may be associated with the activity of SLE and may be one of the factors which cause transient liver abnormalities. [ABSTRACT FROM PUBLISHER]

The pathogenesis of avascular necrosis of bone (ANB) was investigated in 111 patients with systemic lupus erythematosus (SLE) (24 with ANB, 87 without ANB); patients' ages, corticosteroid treatment, clinical and laboratory features associated with SLE, and haemostatic profiles were all taken into account. The mean ages of patients with and without ANB at the time of diagnosis of SLE was 24.1 and 31.2 years respectively. The mean maximal daily dose of prednisolone in the group with ANB was 50.8 mg, which was significantly higher than the dose (41.8 mg) in the group without ANB. Disease features of SLE, such as Raynaud's phenomenon, hyperlipidaemia, nephrotic syndrome, hypertension, and disease activity, were not found to be related to ANB. The percentage of patients who had lupus anticoagulant as well as a shorter activated partial thromboplastin time was greater in those with ANB than in those without. Multiple factors may be involved in the pathogenesis of ANB in SLE, and it is suggested that haemostatic abnormalities, which could be influenced by corticosteroids and young ages, play some part in the development of ANB. [ABSTRACT FROM PUBLISHER]

Breast cancer (BC) is classified into four major histological subtypes, namely luminal A, luminal B, HER2, and basal-like, and its treatment is based on these subtypes. The use of immune checkpoint inhibitors against BC depends on the expression of PD-1/PD-L1. Another tumor immune system-the cGAS-STING pathway-is a potential target for cancer immunotherapy. However, the status of the cGAS-STING pathway in BC has not been fully established. Therefore, we investigated the expression status of the cGAS-STING pathway and immune-related proteins in BC. We classified 111 BCs into six groups-29 hormone receptor-positive carcinomas, 12 HER2+ carcinomas (HER2), 8 luminal-HER2 carcinomas, 26 triple-negative breast carcinomas (TNBCs), 21 lobular carcinomas (LC), and 15 carcinomas with apocrine differentiation (CAD)-and investigated the relationship between BC and tumor immunity via the cGAS-STING pathway using histopathological and immunohistochemical methods. Expression of cGAS was high in CADs (100%) and low in TNBCs (35%); STING-positive lymphocytes were high in TNBC (85%, P = 0.0054). Expression of pSTAT3 was significantly high in patients with TNBC (≥10%, 88%). The proportion of PD-L1-positive tumor cells was higher in TNBCs (54%) than in other BCs (30%). SRGN expression was significantly higher in the TNBC group than in the other BC groups (58%). Tumor immune responses may differ among tumor subtypes. The cGAS-STING pathway may be functional in TNBC and CAD but not in LC. Therefore, targeting the cGAS-STING pathway might be useful in BC, particularly TNBC and CAD., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We report a case of alpha-fetoprotein-producing endometrioid carcinoma (AFP-EC) that originated within an adenomyoma of the uterine corpus. A 76-year-old Japanese woman was incidentally discovered to have a uterine tumor along with multiple lung nodules. Upon surgical removal of the uterus, it was revealed that the tumor was situated within the adenomyoma. The tumor exhibited microfollicular structures and solid growth patterns, with hyaline globules, clear cell glands, and primitive tumor cells. Immunohistochemical analysis indicated the presence of germ cell markers, including AFP, SALL4, and glypican3, leading to final diagnosis of AFP-EC. Histopathologically, AFP-ECs exhibit characteristics similar to those of AFP-producing neoplasms in other organs. Furthermore, a nomenclature issue arises when distinguishing AFP-ECs from yolk sac tumors of the endometrium in older patients due to their shared features. The concept of retrodifferentiation or neometaplasia suggests that "endometrioid carcinoma with yolk sac tumor differentiation" or "endometrioid carcinoma with a primitive phenotype" may serve as more fitting terms for the diverse spectrum of AFP-producing neoplasms in the endometrium. In conclusion, this case underscores the diagnostic challenges posed by AFP-ECs arising from adenomyomas and emphasizes the need for refining the nomenclature and classification of AFP-producing neoplasms within the endometrium., (© 2024. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Generally, sarcomas arising from benign soft tissue are rare. Cardiac myxoma (CM) is a benign tumor, and few reports have described its malignant transformation. Herein, we documented a case of an 89-year-old man with prostate cancer and a 5-year history of a right atrium tumor without Carney complex. The tumor was resected surgically and had a myxomatous or gelatinous appearance. Microscopically, the tumor had two components: a sarcomatous area and myxomatous area. In the myxomatous area, typical myxoma cells were demonstrable and were strongly immunoreactive for immunohistochemistry (IHC) of calretinin. In the sarcomatous area, the epithelioid- to spindle-shaped cells with prominent atypia proliferated densely. The IHC profile of cells in the sarcomatous area was different from that of cells in the myxomatous area; MDM2-positive cells were found only in the sarcomatous area. Especially, the Ki-67 index and number of p53-positive cells in the sarcomatous area were higher than those in the myxomatous area. The transition of the two components was seamless. Thus, we made a diagnosis of CM with malignant transformation corresponding to undifferentiated pleomorphic sarcomas. This case suggests that CM may transform into sarcoma, albeit rarely., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Squamous cell carcinoma (SCC) is a common histological type of lung carcinoma that is associated with interstitial pneumonia (IP). We hypothesized that identifying specific genetic alterations or molecular markers of SCC with IP may aid the development of novel therapeutic strategies for the same. Therefore, in the present study, we aimed to identify tumorigenic genetic alterations and molecular markers in cases of SCC with IP. We included 28 lung SCC cases (14 cases with IP and 14 cases without IP). We performed immunohistochemistry for STAT3, STAT5, and TLE1, and next-generation sequencing was performed using an iSeq 100 system. The panel used in this study targeted 50 cancer-associated genes. Immunohistochemically, the rate of TLE1 positivity was higher in the SCC without IP group (93 %) than in the SCC with IP group (29 %), while that of STAT5 was higher in the SCC with IP group (79 %) than in the SCC without IP group (14 %). STAT3 expression was high in both the groups (SCC with IP, 64 %; SCC without IP, 71 %). Eighteen genes were mutated in more than six samples, and FBXW7 mutation was mainly observed in the SCC with IP group (p < 0.01). Mechanisms underlying tumorigenesis in SCC with IP included STAT5 activation via inflammation, while that in SCC without IP included squamous TLE1-mediated metaplasia. These findings are based on smoking-induced STAT3 activation; therefore, patients with IP who smoke are more likely to have progressive SCC. We also found that FBXW7 mutations may be associated with SCC with IP and keratinization. ERBB4 and KDR mutations were observed in both with or without IP, and these genes may be tumor-related genes in SCC. These molecular markers may help determine the prognoses of patients with SCC with IP and direct the development of treatment approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: A reduced salt intake is a vital lifestyle modification in the management of hypertension. Initiatives aimed at decreasing the intake of salt are based on the preference by humans for a salt taste. Salt intake behavior appears to be affected by the balance between attraction to a low salt taste and aversion to a high salt taste. However, aversion to a high salt taste has not yet been quantitively investigated in both healthy individuals and patients with chronic kidney disease (CKD)., Methods: Assessments of gustatory and aversion thresholds for salt, bitter, sour, and sweet tastes were performed using a stimulant-impregnated test strip in healthy subjects and patients with CKD., Results: In a pilot taste test of 125 healthy subjects, the number of participants with an aversive reaction increased at higher salt concentrations. The threshold for normal taste perception was arbitrarily defined as 10% NaCl, with 47.2% of healthy subjects displaying an aversive reaction. In taste tests performed by 70 patients with CKD, 10% were unable to recognize a salt taste, even at the highest concentration (20% NaCl), suggesting a significant impairment in taste perception in patients with CKD. Only 15.7% of patients with CKD exhibited a normal aversion to NaCl, whereas 78.6% showed the complete loss of aversion to salt., Conclusion: The present results confirmed the anticipated aversive response to a high salt taste in humans and demonstrated its impairment in patients with CKD, implying that patients with CKD have reduced resistance to a high salt intake., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

The immense public health burden of diabetic kidney disease (DKD) has led to an increase in research on the pathophysiology of advanced DKD. The present study focused on the significance of proinflammatory vascular cell adhesion molecule 1 (VCAM1)+ tubules in DKD progression. A retrospective cohort study of DKD patients showed that the percentage of VCAM1+ tubules in kidney samples was correlated with poor renal outcomes. We established an advanced DKD model by partial resection of the kidneys of db/db mice and demonstrated that it closely resembled the human advanced DKD phenotype, with tissue hypoxia, tubular DNA damage, tissue inflammation, and high tubular VCAM1 expression. Luseogliflozin ameliorated tissue hypoxia and proinflammatory responses, including VCAM1+ expression, in tubules. These findings suggest the potential of tubular VCAM1 as a histological marker for poor DKD outcomes. SGLT2 inhibitors may attenuate tissue hypoxia and subsequent tissue inflammation in advanced DKD, thereby ameliorating tubular injury., Competing Interests: T. Kusaba reports receiving commercial research support from Taisho Pharmaceutical and speaker’s bureau honoraria from AstraZeneca., (© 2024 The Author(s).)

Objectives: To examine the perceptions of family medicine among patients attending a family medicine clinic for over 10 years in Japan and explore the unique characteristics of a family medicine which was developed in the local community in northern Japan., Design: Explanatory, sequential mixed-method design comprising a survey by questionnaires and semistructured interviews., Setting: The study was conducted at one of the oldest family medicine primary care clinics in Japan. We surveyed and interviewed participants from November 2019 to March 2020., Participants: 144 patients who have attended a family medicine clinic since April 2009 completed the questionnaires. Semistructured interviews with nine participants were conducted., Results: Among the respondents, 131 (91%) reported having attended a family medicine clinic. In terms of their perceptions of what 'family physicians' do, 42 (35%) stated 'a doctor who treats various diseases with a general view', 34 (29%) stated 'a doctor who treats outpatients and visit patients' houses', and 15 (13%) stated 'a doctor whom one can consult for anything and is familiar with one's family and lifestyle'. The results of the qualitative analysis revealed two themes with regard to patients' perceptions of family medicine: 'seeing the whole person and referring suitably' and 'medical care at home'. Patients' perceptions of family medicine identified in the quantitative study were strongly associated with the characteristics extracted from the qualitative study., Conclusion: Patients attending the family medicine clinic had clear perceptions of what family physicians do. The two major perceptions of the characteristics of family medicine were identified as 'seeing the whole person and referring suitably' and 'medical care at home'., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)