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Background: We experienced a pseudo-outbreak of aspergillosis in a newly constructed COVID-19 ward. Within the first 3 months from the commencement of the ward, six intubated patients of COVID-19 developed probable or possible pulmonary aspergillosis. We suspected an outbreak of pulmonary aspergillosis associated with ward construction and launched air sampling for the investigation of the relationship between these. Methods: The samples were collected at 13 locations in the prefabricated ward and three in the general wards, not under construction, as a control. Results: The results from samples revealed different species of Aspergillus from those detected by the patients. Aspergillus sp. was detected not only from the air samples in the prefabricated ward but also in the general ward. Discussion: In this investigation, we could not find evidence of the outbreak that links the construction of the prefabricated ward with the occurrence of pulmonary aspergillosis. It might suggest that this series of aspergillosis was more likely occurred from fungi that inherently colonized patients, and was associated with patient factors such as severe COVID-19 rather than environmental factors. Once an outbreak originating from building construction is suspected, it is important to conduct an environmental investigation including an air sampling. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Negative myoclonus may present in the early stages of cefepime neurotoxicity. Cefepime neurotoxicity typically presents as reduced consciousness, myoclonus, and seizures; however, negative myoclonus is uncommon. This video shows an older woman with cefepime neurotoxicity that presented as a negative myoclonus of the upper limbs. [ABSTRACT FROM AUTHOR]

Elevation of ALP is an abnormal feature in TAFRO syndrome, but the cause is unknown. This article is the first report that histologically showed intrahepatic cholangitis may be the cause of ALP elevation in TAFRO syndrome. [ABSTRACT FROM AUTHOR]

• Ceftriaxone can cause encephalopathy in patients with end-stage renal disease. • Ceftriaxone-associated encephalopathy (CAE) can develop even at a dose of 1 g/day. • A high blood and cerebrospinal fluid ceftriaxone level may be CAE-related. • Estimation of ceftriaxone level may contribute to an accurate diagnosis. Neurotoxicity is a rare and intolerable adverse effect of ceftriaxone therapy. In most cases, it has been diagnosed on the basis of medical history rather than quantitative blood and cerebrospinal fluid testing. We report the case of a woman aged 78 years with ceftriaxone-associated encephalopathy. She regularly underwent hemodialysis. The patient received intravenous ceftriaxone at a dose of 1 g/day for 10 days for a urinary tract infection, and her consciousness level began to deteriorate during the therapy. Five days after ceftriaxone discontinuation, her symptoms rapidly improved. Thus, ceftriaxone-associated encephalopathy was suspected. Ceftriaxone levels in the blood and cerebrospinal fluid were high while the patient had disturbed consciousness. This case showed that ceftriaxone levels were related to ceftriaxone-associated encephalopathy. Therefore, the estimation of ceftriaxone levels may facilitate an accurate diagnosis. [ABSTRACT FROM AUTHOR]

What is known and objective: Daptomycin‐induced creatinine phosphokinase (CPK) elevation is reported to be associated with its trough level (Ctrough; breakpoint of 24.3 μg/mL). However, even with high‐dose treatment (ie, > 8 mg/kg), the safety of daptomycin treatment is widely demonstrated with low or no significant incidence of CPK elevation or other adverse effects, despite the possibility of Ctrough above 24.3 μg/mL. Therefore, we questioned the clinical significance of Ctrough levels of 24.3 μg/mL. In this study, we retrospectively evaluated the significance of Ctrough in the clinical setting, in addition to completing a retrospective safety assessment of daptomycin utilizing electronic health records. Methods: Patients who had received daptomycin treatment for > 4 days from July 2011 to June 2015 were enrolled. Serum daptomycin levels, including Ctrough and peak (Cpeak), were measured by high‐performance liquid chromatography equipped with a photodiode array. To evaluate the safety, patients' characteristics and relevant laboratory test values were reviewed retrospectively using an electronic medical record system. Results and discussion: A total of 52 therapeutic cases for 46 patients were identified; of these, Ctrough and Cpeak levels were measured in 27 and 28 cases, respectively, and 6 patients received multiple courses of daptomycin treatment. The median age of the 52 patients was 68 years (range: 19‐88 years), and 14 patients initially had an estimated creatinine clearance of less than 30 mL/min. Seven cases indicated a Ctrough of above 24.3 μg/mL; however, none of these presented CPK elevation, which meets with the study definition for abnormality. Furthermore, of the two patients with abnormal CPK elevations, only one patient had a measured Ctrough (of 10.9 μg/mL). Their CPK abnormalities were temporal and did not result in treatment discontinuation. The other four patients discontinued daptomycin treatment due to suspicions of adverse effects. Of the discontinued patients, two had measured Ctrough levels; these were 8.6 and 8.1 μg/mL. All patients with abnormal CPK elevation or treatment discontinuation exhibited Ctrough levels lower than 24.3 μg/mL. In this study, two patients receiving high‐dose daptomycin (ie, 9.4 and 10.0 mg/kg) had observed Ctrough levels similar to patients who received doses of daptomycin < 9 mg/kg. What is new and conclusions: The safety of daptomycin treatment was suggested in this study. Ctrough level of 24.3 μg/mL was not suggested as a significant clinical index for the incidence of CPK elevation, adverse effects or treatment discontinuation. Thus, acceptable tolerability towards higher Ctrough levels than 24.3 μg/mL was also suggested, though further studies are required. On the other hand, low levels of daptomycin in blood were unexpectedly observed in two cases, despite the high‐dose treatments. Accordingly, the monitoring of serum daptomycin levels may also be useful to assess cases in which subtherapeutic levels were achieved. [ABSTRACT FROM AUTHOR]

A 56-year-old man presenting with massive melena and loss of consciousness was diagnosed with an infected thoracoabdominal aneurysm, an aortoduodenal fistula, and Leriche syndrome following an evaluation by computed tomography. Emergency surgery for uncontrolled infection included the reconstruction of the superior mesenteric and bilateral renal arteries using a four-branched graft. The aortoduodenal fistula was resected after omental filling, and an enterostomy was performed for feeding. Intestinal reconstruction was performed in two stages. The patient was discharged on postoperative day 48 and was without evidence of recurrence at 23 months postoperatively. [ABSTRACT FROM AUTHOR]

Penicillium marneffei (Talaromyces marneffei) infection sometimes occurs in HIV‐infected patients in South‐East Asia. However, reports on asymptomatic cases are rare. Herein, we report a case of a 27‐year‐old Burmese HIV‐positive woman with pulmonary penicilliosis. Chest radiography showed a lung mass; however, the patient did not have any respiratory symptoms. Cultures of bronchoalveolar lavage and lung tissue grew P marneffei. The patient was diagnosed with penicilliosis and successfully treated with amphotericin B and itraconazole. Our findings suggest that P marneffei infection should be considered in the differential diagnosis of a lung mass in HIV‐infected patients, even when asymptomatic for respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background The timing of surgical repair for ventricular septal perforation (VSP) is important because patients are susceptible to bleeding from fragile myocardial tissue or residual shunt during the acute phase of acute myocardial infarction (AMI). This study aimed to assess the results of delayed surgery for VSP performed 2 weeks after AMI. Methods In total, 24 consecutive postinfarction patients with VSP (mean age: 72.6 ± 10.4 years; 13 males) underwent operation between May 2003 and June 2016. We postponed surgery during the acute phase and performed an elective surgery if the patient could wait for 2 weeks with support from intra-aortic balloon pumping (IABP) and respiratory management. If we could not control heart failure and organ function worsened during that period, we performed emergency surgery. Postoperative outcomes included complications, 30-day mortality rate, long-term hospital death, reoperation rate, and risk factors for hospital mortality. We examined whether organ function was maintained by delaying the surgery. Results Of the 24 patients, 11 (45.8%) required emergency surgery, and 13 (54.2%) could wait 2 weeks for surgery. The average time from AMI onset to diagnosis of VSP was 4.5 ± 1.6 days, and the average time from VSP diagnosis to surgery was 9.0 ± 6.0 days; 5 patients (20.8%) required resurgery for VSP due to residual shunt, recurrent VSP, or pseudoaneurysm of the left ventricle. The 30-day mortality rate was 4.2% (1 patient), and long-term hospital mortality rate was 12.5% (3 patients). Organ function was maintained in 10 patients (76.9%) who underwent elective surgery, and organ dysfunction was not advanced by delaying the surgery. Conclusions We could delay surgery for an average of 9 days from VSP onset by means of IABP or respiratory management without the deterioration of organ function. The 30-day mortality and long-term outcome were favorable. [ABSTRACT FROM AUTHOR]

Wernicke encephalopathy is caused by vitamin B1 deficiency. It presents as a triad consisting of altered mental status, oculomotor dysfunction, and gait ataxia. Early vitamin B1 administration alleviates symptoms. We present a video of gaze‐evoked nystagmus in an elderly patient with Wernicke encephalopathy. It is often difficult to evaluate the mental and ambulatory states of frail elderly patients with dementia. In such cases, nystagmus is the only useful physical finding in the diagnosis of Wernicke encephalopathy. [ABSTRACT FROM AUTHOR]

Rapidly destructive coxarthrosis is a rare entity of unknown etiology that is characterized by rapid hip joint destruction. Blood tests are thought to be non‐specific. However, we herein show a patient with rapidly destructive coxarthrosis, which was accompanied by fluctuating C‐reactive protein level. [ABSTRACT FROM AUTHOR]

Antihistamines are known risk factors for restless legs syndrome (RLS). However, reports on RLS associated with fexofenadine or its combinations are rare. Here, we report a 30‐year‐old woman with RLS that was induced by fexofenadine/pseudoephedrine. She had been taking fexofenadine/pseudoephedrine for three months and felt a strong urge to move her legs at night, which was relieved by movement. Her condition improved by taking pramipexole, which she discontinued subsequently because of dizziness. One month later, she quitted taking fexofenadine/pseudoephedrine, after which her symptoms disappeared a week later. This case study demonstrates that RLS can be induced by fexofenadine/pseudoephedrine and we should always consider the possibility of drug‐induced RLS. [ABSTRACT FROM AUTHOR]

Neurotoxicity is a rare and intolerable adverse effect associated with levofloxacin therapy, whose diagnosis has mostly been reported based on medical history rather than quantitative measures in the blood. We report a 68-year-old man with levofloxacin-associated encephalopathy and myoclonus with high levels of levofloxacin in the blood and cerebrospinal fluid. After hemodialysis, these decreased, and his symptoms rapidly improved. An electroencephalogram was also normal. This case showed the concentration of levofloxacin to be clearly related to levofloxacin-associated neurotoxicity. Therefore, an estimation of its concentration may contribute to accurate diagnosis. [ABSTRACT FROM AUTHOR]

• Adenosine deaminase (ADA) in the cerebrospinal fluid (CSF) is not specific for diagnosing tuberculous meningitis in HIV infected patients. • Retroviral rebound syndrome can cause meningitis and can also cause ADA elevation in the CSF. • We have to be aware of retroviral rebound syndrome as a cause of ADA elevation in CSF, to avoid unnecessary anti-tuberculous treatment. Adenosine deaminase (ADA) in cerebrospinal fluid (CSF) is considered to be a useful biomarker in differentiating tuberculous meningitis (TBM) from other meningitis in non-HIV patients. However, its specificity decreases in patients with HIV, and other diseases such as cytomegalovirus encephalitis, toxoplasmosis or meningeal lymphomatosis can also elevate ADA in CSF. We here report a rare case of retroviral rebound syndrome in a HIV patient, whose ADA in CSF was elevated. [ABSTRACT FROM AUTHOR]

Platelets store self. agonists such as ADP and serotonin in dense core granules. Although exocytosis of these granules is crucial for hemostasis and thrombosis, the underlying mechanism is not fully understood. Here, we show that incubation of permeabilized platelets with unprenylated active mutant Rab27A-Q78L, wild type Rab27A, and Rab27B inhibited the secretion, whereas inactive mutant Rab27A-T23N and other GTPases had no effects. Furthermore, we affinity-purified a GTPRab27A-binding protein in platelets and identified it as Munc13-4, a homologue of Munc13-1 known as a priming factor for neurotransmitter release. Recombinant Munc13-4 directly bound to GTP-Rab27A and -Rab27B in vitro, but not other GTPases, and enhanced secretion in an in vitro assay. The inhibition of secretion by unprenylated Rab27A was rescued by the addition of Munc13-4, suggesting that Munc13-4 mediates the function of GTP-Rab27. Thus, Rab27 regulates the dense core granule secretion in platelets by employing its binding protein, Munc13-4. [ABSTRACT FROM AUTHOR]

Platelets play critical roles in hemostasis and thrombosis through their aggregation following activation of integrin α[sub IIb]β[sub 3]. However, the molecular mechanism of the integrin activation inside platelets remains largely unknown. Pharmacological experiments have demonstrated that protein kinase C (PKC) plays an important role in platelet aggregation. Because PKC inhibitors can have multiple substrates and given that non-PKC-phorbol ester-binding signaling molecules have been demonstrated to play important roles, the precise involvement of PKC in cellular functions requires re-evaluation. Here, we have established an assay for analyzing the Ca[sup 2+]-induced aggregation of permeabilized platelets. The aggregation of platelets was inhibited by the addition of the arginine-glycine-aspartate-serine peptide, an integrin-binding peptide inhibitor of α[sub IIb]β[sub 3], suggesting that the aggregation was mediated by the integrin. The aggregation was also dependent on exogenous ATP and platelet cytosol, indicating the existence of essential cytosolic factors required for the aggregation. To examine the role of PKC in the aggregation assay, we immunodepleted PKCα and β from the cytosol. The PKC-depleted cytosol lost the aggregation-supporting activity, which was recovered by the addition of purified PKCα. Furthermore, the addition of purified PKCα in the absence of cytosol did not support the aggregation, whereas the cytosol containing less PKC supported it efficiently, suggesting that additional factors besides PKC would also be required. Thus, we directly demonstrated that PKCα is involved in the regulation of Ca[sup 2+]-induced platelet aggregation. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: None declared.

We report a case of a woman in her early 80s with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presented as myalgia mimicking polymyalgia rheumatica (PMR). She had positive results for the Neer and Hawkins-Kennedy impingement tests, and a normal serum creatine kinase (CK) concentration. At first, we suspected PMR; however, the patient did not strictly meet the classification criteria. Electromyography revealed an abnormal myogenic pattern, and muscle MRI revealed intramuscular and fascial hyperintensity. Moreover, chest CT revealed interstitial lung disease, and test results for ANCAs were positive. We diagnosed the patient with ANCA-associated vasculitis based on the criteria and treated her with corticosteroids and rituximab. Thus, ANCA-associated vasculitis can cause muscle involvement without elevation of the CK concentration and mimic PMR., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Streptococcus dysgalactiae subsp. equisimilis (SDSE) commonly causes a variety of infections in older individuals. However, respiratory infections are uncommon. We present the case of an older man with empyema due to SDSE subsequently to bacteraemia. He presented with a 1-day history of fever and laboratory findings revealed an increased white blood cell count and C- reactive protein (CRP) level. Chest CT revealed no infiltration and no pleural effusion. SDSE was detected in the blood cultures. Primary bacteraemia was suspected and antibiotic administration was initiated; however, 2 days later, his right breath sound diminished, and chest radiography revealed right pleural effusion. Thoracentesis yielded cloudy fluid with frank pus; thus, he was diagnosed with empyema due to SDSE, and a drainage tube was placed. Thereafter, his fever improved, and his CRP level decreased. Thus, SDSE can cause empyema probably by haemotological spread of SDSE to the pleura., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors declare no conflict of interest.

A 69-year-old man with a history of anti-synthetase antibody-positive polymyositis and interstitial lung disease (ILD) stable for more than 20 years suddenly developed pulmonary artery hypertension (PAH) with a mean PA pressure of 46 mmHg. At this stage, ILD was mild, but it became acutely exacerbated later, and high-dose corticosteroid and intravenous cyclophosphamide ameliorated both PAH and ILD. The tricuspid regurgitation pressure gradient decreased from 80 to 49 mmHg and ILD recovered almost completely. During a systemic examination, bone metastatic cancer of unknown origin was found. We herein report the relationship between anti-synthetase syndrome (ASS) and PAH as well as ASS and malignancy.

Competing Interests: Competing interests: None declared.

Generalized subcutaneous edema is rare in dermatomyositis. We herein report an 82-year-old woman with dermatomyositis who presented with generalized subcutaneous edema. Three weeks before admission, she first noticed facial edema, and the symptoms exacerbated, with limb edema occurring. On admission, muscle weakness in the limbs and skin rash were noted. Her muscle enzyme levels were elevated, and serum anti-transcriptional intermediary factor 1-γ antibody was detected. She was diagnosed with dermatomyositis and treated with corticosteroids and tacrolimus, which improved her muscle weakness, muscle enzymes, and edema. Thus, generalized subcutaneous edema can occur during dermatomyositis, with facial edema as the initial symptom.

The COVID-19 mainly affects the respiratory system; however, a variety of atypical manifestations of this disease have been also reported. Herein, we report a case of a man in his late 50s with severe COVID-19 presenting with parotitis and sublingual gland sialadenitis. Six days after admission, swelling in the bilateral preauricular and lower jaw areas developed. CT demonstrated parotid and sublingual gland enlargement with surrounding fat stranding, indicating sialadenitis. This case suggests that, in the present COVID-19 pandemic, COVID-19 should be included in the differential diagnosis of sialadenitis and prompt isolation should be considered to reduce the spread of infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)