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A 66-year-old woman presented with sudden-onset pain and bruising in her right middle finger. She had had a similar episode 3 weeks earlier, which had resolved spontaneously. A previously healthy 66-year-old woman presented with sudden-onset pain and bruising in her right middle finger. She had had a similar episode 3 weeks earlier, which had resolved spontaneously within a few days. She did not take any regular medication and reported that she had not had any recent trauma. A physical examination revealed subcutaneous hematoma and swelling with normal capillary refill and sensation. The skin color of the fingers did not change in response to exposure to cold. Laboratory tests revealed a normal platelet count and no coagulopathy. A clinical diagnosis of Achenbach’s syndrome was made. Achenbach’s syndrome is . . .

AbstractObjectiveTo determine whether electronic health record alerts for acute kidney injury would improve patient outcomes of mortality, dialysis, and progression of acute kidney injury.DesignDouble blinded, multicenter, parallel, randomized controlled trial.SettingSix hospitals (four teaching and two non-teaching) in the Yale New Haven Health System in Connecticut and Rhode Island, US, ranging from small community hospitals to large tertiary care centers.Participants6030 adult inpatients with acute kidney injury, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria.InterventionsAn electronic health record based “pop-up” alert for acute kidney injury with an associated acute kidney injury order set upon provider opening of the patient’s medical record.Main outcome measuresA composite of progression of acute kidney injury, receipt of dialysis, or death within 14 days of randomization. Prespecified secondary outcomes included outcomes at each hospital and frequency of various care practices for acute kidney injury.Results6030 patients were randomized over 22 months. The primary outcome occurred in 653 (21.3%) of 3059 patients with an alert and in 622 (20.9%) of 2971 patients receiving usual care (relative risk 1.02, 95% confidence interval 0.93 to 1.13, P=0.67). Analysis by each hospital showed worse outcomes in the two non-teaching hospitals (n=765, 13%), where alerts were associated with a higher risk of the primary outcome (relative risk 1.49, 95% confidence interval 1.12 to 1.98, P=0.006). More deaths occurred at these centers (15.6% in the alert group v 8.6% in the usual care group, P=0.003). Certain acute kidney injury care practices were increased in the alert group but did not appear to mediate these outcomes.ConclusionsAlerts did not reduce the risk of our primary outcome among patients in hospital with acute kidney injury. The heterogeneity of effect across clinical centers should lead to a re-evaluation of existing alerting systems for acute kidney injury.Trial registrationClinicalTrials.gov NCT02753751.

There have been few reports on the diagnostic performance of soluble interleukin-2 receptor (sIL-2R) for lymphoma. A cross-sectional study was conducted at a university hospital; all patients who were admitted to the Division of General Internal Medicine and underwent serum sIL-2R testing were included. Patients were divided into two groups based on the presence of fever (≥ 38.0 °C). Among 602 patients, 421 had fever and 76 were diagnosed with lymphoma (48 of the 76 were in the febrile group). In all patients, the area under the receiver operating characteristic curve (AUROC) of sIL-2R for the diagnosis of lymphoma was 0.81 [95% confidence interval (CI), 0.75–0.87]. The AUROC was significantly higher in the febrile group (0.88; 95% CI, 0.81–0.94) than in the afebrile group (0.75; 95% CI, 0.65–0.85). In the febrile group, the sensitivity and specificity were 81.2% and 82.3%, respectively, with an optimal cutoff value of 3,250 U/mL. In the afebrile group, they were 89.3% and 54.9%, respectively, with a cutoff value of 868 U/mL. Serum sIL-2R showed high performance as an adjunctive diagnostic marker for lymphoma, particularly among febrile patients. Different cutoff values should be used for patients with and without fever to maximize diagnostic performance.

Acute kidney injury (AKI) is an adverse event that carries significant morbidity. Given that interventions after AKI occurrence have poor performance, there is substantial interest in prediction of AKI prior to its diagnosis. However, integration of real-time prognostic modeling into the electronic health record (EHR) has been challenging, as complex models increase the risk of error and complicate deployment. Our goal in this study was to create an implementable predictive model to accurately predict AKI in hospitalized patients and could be easily integrated within an existing EHR system. We performed a retrospective analysis looking at data of 169,859 hospitalized adults admitted to one of three study hospitals in the United States (in New Haven and Bridgeport, Connecticut) from December 2012 to February 2016. Demographics, medical comorbidities, hospital procedures, medications, and laboratory data were used to develop a model to predict AKI within 24 hours of a given observation. Outcomes of AKI severity, requirement for renal replacement therapy, and mortality were also measured and predicted. Models were trained using discrete-time logistic regression in a subset of Hospital 1, internally validated in the remainder of Hospital 1, and externally validated in Hospital 2 and Hospital 3. Model performance was assessed via the area under the receiver-operator characteristic (ROC) curve (AUC). The training set cohort contained 60,701 patients, and the internal validation set contained 30,599 patients. External validation data sets contained 43,534 and 35,025 patients. Patients in the overall cohort were generally older (median age ranging from 61 to 68 across hospitals); 44%-49% were male, 16%-20% were black, and 23%-29% were admitted to surgical wards. In the training set and external validation set, 19.1% and 18.9% of patients, respectively, developed AKI. The full model, including all covariates, had good ability to predict imminent AKI for the validation set, sustained AKI, dialysis, and death with AUCs of 0.74 (95% CI 0.73-0.74), 0.77 (95% CI 0.76-0.78), 0.79 (95% CI 0.73-0.85), and 0.69 (95% CI 0.67-0.72), respectively. A simple model using only readily available, time-updated laboratory values had very similar predictive performance to the complete model. The main limitation of this study is that it is observational in nature; thus, we are unable to conclude a causal relationship between covariates and AKI and do not provide an optimal treatment strategy for those predicted to develop AKI. In this study, we observed that a simple model using readily available laboratory data could be developed to predict imminent AKI with good discrimination. This model may lend itself well to integration into the EHR without sacrificing the performance seen in more complex models.

Background General medicine (GM) was formally recognized as a specialty in Japan in 2018 to address the need for primary care. Understanding factors influencing GM career choices is critical for recruitment. However, the reform’s impact on career decision-making remains unclear. This study examined factors influencing GM career choices following the introduction of the new specialty certification and identified challenges in this field. Methods A secondary analysis of national survey data from the Ministry of Health, Labour and Welfare’s questionnaire (2018–2020) for clinical training graduates examined post-training career intentions of specializing in GM, focusing on factors influencing choices such as demographics, education, and training contexts. Multivariable logistic regression was conducted with post-training GM preference as the dependent variable. The results are expressed as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results Among 16,674 complete responses, 59% of the 229 individuals initially interested in GM actually pursued it post-training. Positive factors included regional quotas (aOR 3.10, 95% CI 1.12–8.56), ≤ 1 month GM rotation (aOR 3.39, 95% CI 1.03–11.14), > 2 months community medicine (CM) rotations (aOR 13.35, 95% CI 2.40–76.58), desire for primary care skills (aOR 4.85, 95% CI 2.01–11.73), and community contribution aspirations (aOR 6.88, 95% CI 2.75–17.21). The most influential negative factor was perceived ease of specialization maintenance (aOR 0.01, 95% CI 0.00–0.12). Among 16,445 individuals who preferred other specialties, 86 switched to GM. Extended GM rotations (1<–≤2 months: aOR 3.54, 95% CI 2.06–6.09; >2 months: aOR 7.41, 95% CI 4.56–12.04) increased the likelihood of switching. Academic interest (aOR 0.36, 95% CI 0.23–0.58) and perceived ease of maintaining specialization (aOR 0.13, 95% CI 0.03–0.54) were negative factors. Conclusions GM rotations may positively influence career choices, with longer CM rotations potentially increasing interest. Establishing clear career paths and educating resident physicians about the academic characteristics of GM remain challenging despite its recognition as a specialty.

The reliability of GPT-4, a state-of-the-art expansive language model specializing in clinical reasoning and medical knowledge, remains largely unverified across non-English languages. This study aims to compare fundamental clinical competencies between Japanese residents and GPT-4 by using the General Medicine In-Training Examination (GM-ITE). We used the GPT-4 model provided by OpenAI and the GM-ITE examination questions for the years 2020, 2021, and 2022 to conduct a comparative analysis. This analysis focused on evaluating the performance of individuals who were concluding their second year of residency in comparison to that of GPT-4. Given the current abilities of GPT-4, our study included only single-choice exam questions, excluding those involving audio, video, or image data. The assessment included 4 categories: general theory (professionalism and medical interviewing), symptomatology and clinical reasoning, physical examinations and clinical procedures, and specific diseases. Additionally, we categorized the questions into 7 specialty fields and 3 levels of difficulty, which were determined based on residents' correct response rates. Upon examination of 137 GM-ITE questions in Japanese, GPT-4 scores were significantly higher than the mean scores of residents (residents: 55.8%, GPT-4: 70.1%; P<.001). In terms of specific disciplines, GPT-4 scored 23.5 points higher in the \"specific diseases,\" 30.9 points higher in \"obstetrics and gynecology,\" and 26.1 points higher in \"internal medicine.\" In contrast, GPT-4 scores in \"medical interviewing and professionalism,\" \"general practice,\" and \"psychiatry\" were lower than those of the residents, although this discrepancy was not statistically significant. Upon analyzing scores based on question difficulty, GPT-4 scores were 17.2 points lower for easy problems (P=.007) but were 25.4 and 24.4 points higher for normal and difficult problems, respectively (P<.001). In year-on-year comparisons, GPT-4 scores were 21.7 and 21.5 points higher in the 2020 (P=.01) and 2022 (P=.003) examinations, respectively, but only 3.5 points higher in the 2021 examinations (no significant difference). In the Japanese language, GPT-4 also outperformed the average medical residents in the GM-ITE test, originally designed for them. Specifically, GPT-4 demonstrated a tendency to score higher on difficult questions with low resident correct response rates and those demanding a more comprehensive understanding of diseases. However, GPT-4 scored comparatively lower on questions that residents could readily answer, such as those testing attitudes toward patients and professionalism, as well as those necessitating an understanding of context and communication. These findings highlight the strengths and limitations of artificial intelligence applications in medical education and practice.

Chickens in free-range environments are at risk of exposure to various pathogens, such as filarioids transmitted via hematophagous vectors. However, the study of filarioids in poultry has been largely neglected compared to the extensive studies focused on viruses, bacteria, and protozoa. Here, we performed histological and molecular investigations of the filarioids detected in domestic chickens from two different flocks in Hiroshima Prefecture, Japan. In the first case, adult worms were present in the pulmonary artery and right ventricle, and microfilariae were present in multiple organs of deceased chickens. In the second case, similar filarioids were detected in the organs and blood of one necropsied layer. Phylogenetic analysis using 18S rRNA gene fragments positioned the filarioid in the same clade as that of Onchocercidae sp., previously identified in a deceased chicken from Chiba Prefecture, Japan, that is located 500 km away from Hiroshima Prefecture. Based on 28S rRNA and mitochondrial COI gene fragments, the filarioid was positioned distinctly from previously reported genera of avian filarioids. These results suggest that the filarioids are potentially associated with the health burden on domestic chickens and belong to the genus Paronchocerca . Furthermore, we developed a nested PCR assay targeting mitochondrial COI and detected the parasite DNA from the biting midge Culicoides arakawae captured near the flock, suggesting that it serves as a vector. Our findings fill the knowledge gap regarding avian filarioids, laying the groundwork for future studies examining the epidemiology, life cycle, and species diversity of this neglected parasite group.

DNA can adopt various structures besides the B-form. Among them, cruciform structures are formed on inverted repeat (IR) sequences. While cruciform formable IRs (CFIRs) are sometimes found in regulatory regions of transcription, their function in transcription remains elusive, especially in eukaryotes. We found a cluster of CFIRs within the mouse Pou5f1 enhancer. Here, we demonstrate that this cluster or some member(s) plays an active role in the transcriptional regulation of not only Pou5f1, but also Sox2, Nanog, Klf4 and Esrrb. To clarify in vivo function of the cluster, we performed genome editing using mouse ES cells, in which each of the CFIRs was altered to the corresponding mirror repeat sequence. The alterations reduced the level of the Pou5f1 transcript in the genome-edited cell lines, and elevated those of Sox2, Nanog, Klf4 and Esrrb. Furthermore, transcription of non-coding RNAs (ncRNAs) within the enhancer was also upregulated in the genome-edited cell lines, in a similar manner to Sox2, Nanog, Klf4 and Esrrb. These ncRNAs are hypothesized to control the expression of these four pluripotency genes. The CFIRs present in the Pou5f1 enhancer seem to be important to maintain the integrity of ES cells.

Background The aim of this study was to explore what experiences certified primary care physicians (PCPs) in Japan found meaningful in their work. Method Between October 2021 and February 2022, semi-structured interviews were conducted with Japan Primary Care Association (JPCA)-certified family physicians or JPCA Diplomates in primary care who were working at clinics or small hospitals in Japan regarding “work experiences that they felt were meaningful as physician’s work”. The interviews were conducted face-to-face or via video call. The data obtained were transcribed verbatim and data analysis was conducted using inductive thematic analysis. Results Fourteen physicians participated in the interview survey. Six themes were identified regarding work experiences that PCPs found meaningful: 1) management of diverse health problems, 2) comprehensive approach to patients, their families, and their issues, 3) trust relationships with patients built by continuity, 4) experience supporting patients with complex problems through interprofessional collaboration, 5) contribution to healthcare provider and medical student education, and 6) contribution to the community and society. Conclusion PCPs appear to find meaning in their work through two main pathways. First, they improve their own clinical abilities through practice. Second, they experience fulfillment by contributing to patients and the broader community. This clarification of the specific experiences of PCPs that are related to the meaning of work could potentially encourage PCPs working in various settings.

Virulent fowl adenovirus serotype 4 (FAdV-4) causes hydropericardium syndrome (HPS) with high mortality in chickens, leading to significant economic losses to the poultry industry. The development of an effective vaccine is essential for successful disease control. Here, we produced recombinant fiber-1 protein of FAdV-4, isolated from a Japanese HPS outbreak strain, JP/LVP-1/96, using a baculovirus expression system and evaluated its immunogenicity and protective efficacy. Recombinant fiber-1 protein induced high levels of neutralizing antibodies in immunized chickens, which were maintained for a minimum of 10 weeks. After being challenged with the virulent FAdV-4 strain JP/LVP-1/96, the immunized chickens did not exhibit clinical signs of infection or histopathological changes, there was a significant reduction in the viral load in various organs and total serum proteins, and albumin levels did not decline. These results suggest that the recombinant fiber-1 protein produced in this study can serve as a subunit vaccine to control HPS in chickens.