Clinical effectiveness of molnupiravir in patients with COVID-19 undergoing haemodialysis.

BACKGROUND: Molnupiravir is an essential oral antiviral agent against coronavirus disease 2019 (COVID-19); however, its real-world effectiveness has not been evaluated in patients undergoing haemodialysis (HD). METHODS: This multi-centre retrospective study, involving 225 patients undergoing HD with initially mild or asymptomatic COVID-19, was conducted to compare the risks of 30-day COVID-19-related acute care visits between patients receiving and not receiving molnupiravir. Patients who received molnupiravir were stratified by rapid antigen detection (RAD) test results on day 7 after disease onset to assess whether rapid molnupiravir introduction accelerated viral clearance. RESULTS: Thirty-day COVID-19-related acute care visits were reported in 9.41% and 21.74% of the molnupiravir and control groups, respectively, and use of molnupiravir markedly reduced the risk of acute care visits after adjusting for baseline characteristics via propensity score weighting [hazard ratio 0.218, 95% confidence interval (CI) 0.074-0.642; P=0.006]. The tolerability of molnupiravir in the enrolled patients was generally acceptable, with only 11.88% of molnupiravir users reporting mild adverse events. Moreover, rapid initiation of molnupiravir within 1 day of COVID-19 onset was an independent predictor of conversion to a negative RAD test result on day 7 after disease onset (odds ratio 6.207, 95% CI 2.509-15.358; P<0.001). CONCLUSIONS: Molnupiravir is well tolerated and decreases the medical needs in patients with COVID-19 undergoing HD. Furthermore, the rapid initiation of molnupiravir accelerates viral clearance in patients with COVID-19 undergoing HD. These findings highlight the therapeutic role of molnupiravir for this vulnerable population.

Using mass spectrometry imaging to visualize age-related subcellular disruption.

Metabolic homeostasis balances the production and consumption of energetic molecules to maintain active, healthy cells. Cellular stress, which disrupts metabolism and leads to the loss of cellular homeostasis, is important in age-related diseases. We focus here on the role of organelle dysfunction in age-related diseases, including the roles of energy deficiencies, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, changes in metabolic flux in aging (e.g., Ca2+ and nicotinamide adenine dinucleotide), and alterations in the endoplasmic reticulum-mitochondria contact sites that regulate the trafficking of metabolites. Tools for single-cell resolution of metabolite pools and metabolic flux in animal models of aging and age-related diseases are urgently needed. High-resolution mass spectrometry imaging (MSI) provides a revolutionary approach for capturing the metabolic states of individual cells and cellular interactions without the dissociation of tissues. mass spectrometry imaging can be a powerful tool to elucidate the role of stress-induced cellular dysfunction in aging.

The efficacy and safety of cupping as complementary and alternative therapy for metabolic syndrome: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to assess the efficacy and safety of cupping therapy in patients with metabolic syndrome (MetS). METHODS: This systematic review focused on patients with MetS and included randomized controlled trials (RCTs) that compared the effects of cupping therapy with control groups. A total of 12 electronic databases were searched from inception until February 03, 2023. The main outcome after the meta-analysis was waist circumference; the others included anthropometric variables, blood pressure, lipid profile, fasting blood glucose level, and high-sensitivity C-reactive protein level. The incidence of adverse events and the follow-up courses were also evaluated. Risk of bias (ROB) was evaluated using ROB 2.0 from the Cochrane Handbook. RESULTS: This systematic review included five studies involving 489 patients. Some risks of bias were also identified. The meta-analysis revealed a statistically significance in waist circumference (MD = -6.07, 95% CI: -8.44 to -3.71, P < .001, I2 = 61%, τ2 = 3.4), body weight (MD = -2.46, 95% CI: -4.25 to -0.68, P = .007, I2 = 0%, τ2 = 0) and body mass index (MD = -1.26, 95% CI: -2.11 to -0.40, P = .004, I2 = 0%, τ2 = 0) between the cupping therapy and control groups. However, there were no significant results in total fat percentage and blood pressure values. Regarding biochemical markers, cupping significantly lowered the concentration of low-density lipoprotein cholesterol (MD = -3.98, 95% CI: -6.99 to -0.96, P = .010, I2 = 0%, τ2 = 0) but had no significant effect on total cholesterol, triglyceride, high-density lipoprotein cholesterol, fasting blood glucose, and high-sensitivity C-reactive protein. 3 RCTs reported no adverse events. CONCLUSIONS: Despite some ROB and low to substantial heterogeneity of the included studies, cupping therapy can be considered a safe and effective complementary intervention for reducing waist circumference, body weight, body mass index, and low-density lipoprotein cholesterol in patients with MetS. In the future, well-designed, high-quality, rigorous methodology, and long-term RCTs in this population are required to assess the efficacy and safety of cupping therapy.

Real-World Effectiveness of SARS-CoV-2 Vaccine Booster in Hemodialysis Patients with COVID-19 Receiving Molnupiravir.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine booster is one of the most essential strategies against coronavirus disease 2019 (COVID-19) in the era of emerging variants. However, the effectiveness of SARS-CoV-2 vaccine boosters has not much been investigated in hemodialysis (HD) patients receiving oral antiviral agents. In this retrospective study involving 258 HD patients with COVID-19 receiving molnupiravir, we stratified the study cohort according to vaccination status and compared the baseline characteristics and risks of 30-day composite events (COVID-19-related acute care visits, hospitalization, or mortality) among groups. Our analysis demonstrated that the SARS-CoV-2 vaccine boosters markedly decreased the risk of composite events in HD patients (hazard ratio (95% confidence interval), 0.163 (0.063-0.423) for three vs. ≤ two doses of vaccination, p < 0.001; 0.309 (0.115-0.830) for four vs. ≤ two doses of vaccination, p = 0.020). The benefits of vaccine boosters were similar between patients receiving mRNA-based and protein-based boosters and between those with post-booster intervals of ≤ 120 and > 120 days. In conclusion, for HD patients with initially mild or asymptomatic COVID-19 receiving molnupiravir, the benefits of SARS-CoV-2 vaccine boosters are prominent, irrespective of booster vaccine types.

Chondroma of the urinary bladder: A case report.

RATIONALE: Chondromas are benign tumors comprising cartilaginous tissue that commonly occur in the small bones of the hands and feet. Chondromas are extremely rare in extraskeletal soft tissues, and only six cases of bladder chondromas have been reported thus far. PATIENT CONCERNS: A 75-year-old woman presented with abdominal pain and urinary symptoms, including increased frequency and a weak stream. DIAGNOSIS: Cystoscopy revealed a well-defined bladder mass over the anterior bladder wall. The pathology report showed neoplastic chondrocytes within the hyalinized and focal myxoid matrix, and immunopositivity for S-100, leading to the seventh known diagnosis of bladder chondroma. INTERVENTIONS: The tumor was endoscopically resected. The postoperative stay was uneventful, and 5 days later, the patient was discharged after the removal of the urinary catheter. OUTCOMES: One month after surgery, repeated cystoscopy showed no recurrence of the bladder tumor, and the patient reported improvement in urinary symptoms and relief of lower abdominal pain. LESSONS: Chondromas of the urinary bladder can present as urinary symptoms and abdominal pain in older patients. Transurethral resection is the treatment of choice.

Recommendations and guidelines for the treatment of infections due to multidrug resistant organisms.

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

Intraoperative Sentinel Lymph Node Imprint Cytology Diagnosis in Breast Cancer Patients by General Surgical Pathologists: A Single-Institution Experience of 4327 Cases.

Context: Sentinel lymph node (SLN) biopsy is the standard of care for breast cancer (BC) patient staging. The axillary node status can be evaluated by frozen section (FS) or imprint cytology (IC). Despite the major disadvantages of tissue loss and freezing artifact in FS, many pathologists consider SLN IC a more difficult task requiring special expertise and prefer FS to IC. Aims: To conduct a large cohort study to evaluate the results of intraoperative SLN IC, compare them with those of FS and permanent section (PS), and determine the best method for general pathologists. Settings and Design: A very large cohort study with many pathologists engaged was designed and the diagnostic results were compared. Materials and Methods: With 12 pathologists engaged, we conducted the largest patient cohort study of SLN IC to date, including 4,327 consecutive BC patients undergoing SLN biopsy during the past 15 years. The touch imprints were stained using three different methods and evaluated. The PS was used as the gold standard for evaluation. Statistical Analysis: The false positivity, false negativity, accuracy, sensitivity, and specificity of the IC and FS for each pathologist were evaluated and compared. Results: Our results showed an overall sensitivity of 82.7%, specificity of 99.3%, and an accuracy rate of 95.9% for SLN IC, which were comparable to those of FS. The accuracy rate did not correlate with the length of working experience and the staining method. Conclusions: Intraoperative hematoxylin and eosin (H&E)-stained IC preparation was found to be the best SLN examination method for general pathologists.

A multicenter cohort study of severe dengue and critically ill influenza patients with elevated cardiac troponin-I: Difference clinical features and high mortality.

BACKGROUND: As cardiac involvement can cause serious complications and death, understanding its role in acute dengue and influenza virus infections is important. METHODS: We provide a comparative evaluation of severe dengue and critically ill influenza patients with elevated cardiac troponin-I (cTnI) from 2014 to 2019. Inclusion criteria included patients in which cTnI test were ordered. Patient without cTnI test was excluded. RESULTS: During the study period, 82 (41 severe dengue and 41 critically ill influenza) patients had cTnI elevations, and 81 (35 severe dengue and 46 critically ill influenza) patients had a single normal cTnI test. Severe dengue patients with cTnI elevations had a significantly higher incidences of acute kidney injury, gastrointestinal bleeding, early mortality (≤7 after illness onset) and in-hospital mortality than those with severe dengue and single normal cTnI test. Significantly higher aspartate aminotransferase (AST) levels and higher incidence of gastrointestinal bleeding was observed in critically ill influenza patients with cTnI elevations compared to critically ill influenza patients with single normal cTnI measurement. Of the patients with cTnI elevations, the early and in-hospital mortality rates were 53.6% and 65.8%, respectively, in severe dengue patients, and 7.3% and 46.3%, respectively, in critically ill influenza patients. Significantly higher early mortality rates were observed in severe dengue patients with elevated cTnI levels than in critically ill influenza patients with cTnI elevations. Critically ill influenza patients with elevated cTnI levels had significantly higher incidences of pneumonia, pneumothorax, and bacteremia than severe dengue patients with cTnI elevations. Multivariate analysis revealed elevated AST (>1000U/L) (95% confidence interval [CI]: 1.690-143.174) was an independent risk factor for in-hospital mortality in severe dengue patients with elevated cTnI levels. Leukocytosis (95% CI: 1.079-1.124) and thrombocytopenia (95% CI: 2.739-5.821) were independently correlated with in-hospital mortality in critically ill influenza patients with cTnI elevations. CONCLUSIONS: Differences in clinical features between severe dengue and critically ill influenza patients with cTnI elevations. High early mortality rate was observed in severe dengue patients with cardiac involvement. In contrast, most critically ill influenza patients died ≥2 weeks after the onset of illness, regardless of cTnI elevations. Our report has important clinical implications for the timely recognition and management of cardiac complication in patients with acute dengue and influenza virus infections.

Epidemiology and risk factors of scrub typhus in Taiwan: A nationwide database study from 1996 to 2014.

BACKGROUND: Scrub typhus (ST) is one of the most underdiagnosed, potentially fatal febrile diseases in the Asia-Pacific region. We conducted a comprehensive review of the risk factors of ST over 19 years using data from a nationwide database. METHODS: We used data on ST from the nationwide database of the Taiwan Centers for Disease Control from 1996 to 2014 to analyse the incidence rates and relative risks of ST according to different regions. The trends of incidence rates over the study period were also evaluated. The distribution of confirmed ST cases was mapped using geographic information system software. The characteristics of confirmed ST cases and non-ST cases (cases with suspected ST but negative test findings) were compared. RESULTS: Among the 38,127 reported cases, there were 6,791 (17.8%) confirmed ST cases. The overall incidence rate of ST in Taiwan was 1.49 per 100,000 residents per year. The trend of incidence rates increased over time. The Island region had the highest incidence rate (56.55 per 100,000 residents per year), followed by the Eastern region (15.13 per 100,000 residents per year). More confirmed ST cases were distributed in mountainous areas of Taiwan Main Island and Island region. Compared to non-ST cases, individuals with confirmed ST were younger (median [interquartile range] age: 44 [26-57] years versus 45 [30-60] years, p < .001) and more likely to engage in at-risk occupations (29.4% versus 13.3%, p < .001), including farming and animal husbandry (16.6% versus 9.0%, p < .001) and the armed forces (12.3% versus 3.5%, p < .001); however, they had a lower rate of animal contact (12.8% versus 20.1%, p < .001). CONCLUSIONS: ST is an endemic disease in Taiwan, particularly in the Island region, Eastern region and mountainous areas. Patients engaged in at-risk occupations and presenting with acute febrile diseases should undergo investigations for ST.

Association between Enzyme-Linked Immunosorbent Assay-Measured Kidney Injury Markers and Urinary Cadmium Levels in Chronic Kidney Disease.

Cadmium exposure is associated with chronic kidney disease (CKD), but the optimal biomarker for early cadmium-associated nephrotoxicity in low-level exposure has not yet been established. We conducted a cross-sectional investigation involving 167 CKD patients stratified according to tertiles of urinary cadmium levels (UCd), in which enzyme-linked immunosorbent assay (ELISA)-measured novel renal biomarkers were utilized to assess the extent of renal injury associated with cadmium burden. In the analyses, urinary kidney injury molecule-1 (KIM-1) levels and age were the independent factors positively correlated with UCd after adjusting for covariates in non-dialysis-dependent CKD patients (high vs. low UCd, odds ratio (95% confidence interval), 1.0016 (1.0001-1.0032), p = 0.043, and 1.0534 (1.0091-1.0997), p = 0.018). Other conventional and novel renal biomarkers, such as serum creatinine, estimated glomerular filtration rate, CKD staging, urinary protein/creatinine ratio, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), and urinary epidermal growth factor (EGF) were not independently correlated with UCd in the analyses. In conclusion, our study found that the ELISA-measured urinary KIM-1 level could serve as an early renal injury marker in low-level cadmium exposure for non-dialysis-dependent CKD patients. In addition, age was an independent factor positively associated with UCd in this population.

The epidemiology, characteristics and outbreaks of human leptospirosis and the association with animals in Taiwan, 2007-2014: A nationwide database study.

BACKGROUND: Leptospirosis (LS) is a neglected tropical zoonosis of global importance. A nationwide investigation of characteristics, epidemiology, risk factors and outbreak is crucial for awareness of this disease. METHODS: A nationwide database of reported LS cases from October 2007 to December 2014 obtained from the Centers for Disease Control, Taiwan, was analysed. Geographic information system software was used to map the distribution of confirmed LS cases and pigs. Cross-matching with the databases of Q fever, scrub typhus and murine typhus was conducted to identify possible coinfections. RESULTS: A total of 10,917 reported cases of LS were recorded in the database, which included 665 (6.1%) confirmed LS and 10,252 (93.9%) non-confirmed LS cases. The major residences of confirmed LS were the Kaohsiung-Pingtung (248, 37.3%) and Taipei (174, 26.2%) regions. The average annual incidence was 0.4/100,000 people. Compared with non-confirmed LS cases, confirmed LS cases had significantly higher percentages of male gender (83.6% vs. 67.9%, p < .001), high-risk occupations (farmer, animal husbandry or veterinarian) (24.8% vs. 13.7%, p < .001), residence in the Kaohsiung-Pingtung region (37.3% vs. 19.6%, p < .001) and exposure to rats (8.6% vs. 4.9%, p = .001) or pigs (9.4% vs. 1.9%, p < .001) but a lower mean age (47.8 ± 15.1 vs. 51.±18.5 years old). Rat and pig exposure trends were found in the northern and southern regions, respectively. Distribution of LS was consistent with pigs, and one outbreak associated with flooding and pigs occurred in the Pingtung region in 2009. Twenty-three and four patients with LS were coinfected with scrub typhus and Q fever, respectively. CONCLUSIONS: LS is an endemic disease in Taiwan, particularly in the Kaohsiung-Pingtung and Taipei regions. High-risk occupations and animal exposure history are important for the clinical presumptive diagnosis of LS, particularly for rats in northern Taiwan and pigs in southern Taiwan. Although uncommon, clinicians should be aware of coinfection of LS with endemic rickettsial diseases.

Clinicoepidemiologic characteristics of scrub typhus and murine typhus: A multi-center study in southern Taiwan.

BACKGROUND: This study aimed to offer key features to differentiate scrub typhus (ST) and murine typhus (MT) at the early stage of the diseases and provide clinicoepidemiologic characteristics of ST and MT in southern Taiwan, a region where both diseases are endemic. Comparison of doxycycline treatment efficacy between the two diseases by matching disease severity and delayed treatment had never been investigated. METHODS: We reviewed the medical records of cases of ST and MT in four hospitals in southern Taiwan. Propensity-score matching was used to analyze the defervescence curves between patients with doxycycline-treated ST and MT by log-rank test. RESULTS: Between 2004 and 2016, 265 ST and 63 MT cases were diagnosed. The number of cases of ST was significantly related to temperature (Rs = 0.77) and rainfall (Rs = 0.63). Island area exposure, arthropod bite, eschar, and lymphadenopathy were only recorded in ST patients. Multivariate analysis revealed that mountainous area exposure (odds ratio [OR], 11.0; 95% confidence interval [CI], 4.4-27.2) was an independent predictor for ST, while contact with rats (OR, 8.4; 95% CI, 3.3-21.3) was that for MT. After propensity-score matching, there was no difference in defervescence curves between these two rickettsioses treated with doxycycline (p = 0.24). CONCLUSION: In the present study, island area exposure, arthropod bite, eschar, and lymphadenopathy were unique manifestations of ST. Mountainous area exposure is a predictive factor for ST, while contact with rats predicted MT. There was no difference in defervescence time between these two rickettsioses after doxycycline treatment.

Cellular neurothekeoma with melanocytosis.

Cellular neurothekeoma (CNT) is a benign dermal tumor mainly affecting the head and neck and the upper extremities. It is characterized histologically by interconnecting fascicles of plump spindle or epithelioid cells with ample cytoplasm infiltrating in the reticular dermis. The histogenesis of CNT has been controversial, although it is generally regarded as an immature counterpart of classic/myxoid neurothekeoma, a tumor with nerve sheath differentiation. Two rare cases of CNT containing melanin-laden cells were described. Immunohistochemical study with NKI/C3, vimentin, epithelial membrane antigen, smooth muscle antigen, CD34, factor XIIIa, collagen type IV, S100 protein and HMB-45 was performed. Both cases showed typical growth pattern of CNT with interconnecting fascicles of epithelioid cells infiltrating in collagenous stroma. One of the nodules contained areas exhibiting atypical cytological features. Melanin-laden epithelioid or dendritic cells were diffusely scattered throughout one nodule, and focally present in the peripheral portion of the other nodule. Both nodules were strongly immunoreactive to NKI/C3 and vimentin, but negative to all the other markers employed. CNT harboring melanin-laden cells may pose diagnostic problems because of their close resemblance to nevomelanocytic lesions and other dermal mesenchymal tumors. These peculiar cases may also provide further clues to the histogenesis of CNT.

Characteristics of cranial aneurysmal bone cyst on computed tomography and magnetic resonance imaging.

Aneurysmal bone cysts are benign bone tumors that most commonly occur in people younger than 30 years. The cysts are most often found in the metaphyses of long bones and rarely affect the skull. We present a 54-year-old woman with a rapidly enlarging mass in the left occipital region that caused tenderness for 2 weeks. Computed tomography (CT) revealed an expansile, osteolytic lesion with characteristic soap-bubble appearance and fluid-fluid levels. Magnetic resonance images showed a dark rim surrounding the lesion, as well as multilocular spaces with fluid-fluid levels. The tumor was soft, fragile, and pulsatile during surgery. The patient was treated with en bloc resection of the tumor with cranioplasty. Follow-up CT 5 months later showed no evidence of recurrence.