Investigation of cardiorenal outcomes and incidence of genitourinary tract infection after combined SGLT2 inhibitor and ACEI/ARB use in patients with chronic kidney disease stages 3-5: A real-world retrospective cohort study in Taiwan.

Background: Sodium‒glucose cotransporter-2 (SGLT2) inhibitors offer glycaemic and cardiorenal benefits in the early stage of chronic kidney disease (CKD). However, the use of SGLT2 inhibitors may increase the risk of genitourinary tract infection (GUTI). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may also cause deterioration of kidney function. The long-term follow-up of cardiorenal outcomes and GUTI incidence in patients with advanced CKD receiving SGLT2 inhibitors combined with ACEIs/ARBs should be further investigated. Methods: We analysed data from 5,503 patients in Taiwan's Taipei Medical University Research Database (2016-2020) who were part of a pre-end-stage renal disease (ESRD) program (CKD stages 3-5) and received ACEIs/ARBs. SGLT2 inhibitor users were matched 1:4 with nonusers on the basis of sex, CKD, and program entry duration. Results: The final cohort included 205 SGLT2 inhibitor users and 820 nonusers. SGLT2 inhibitor users experienced a significant reduction in ESRD/dialysis risk (aHR = 0.35, 95% CI = 0.190.67), and SGLT2 inhibitor use was not significantly associated with acute kidney injury or acute kidney disease risk. Among SGLT2 inhibitor users, those with a history of cardiovascular disease (CVD) had greater CVD rates. Conversely, those without a CVD history had lower rates of congestive heart failure, arrhythmia, acute pulmonary oedema, and acute myocardial infarction, although the differences were not statistically significant. Notably, SGLT2 inhibitor usage was associated with a greater GUTI incidence (aHR = 1.78, 95% CI = 1.122.84) shortly after initiation, irrespective of prior GUTI history status. Conclusion: Among patients with CKD stages 3-5, SGLT2 inhibitor use was linked to increased GUTI incidence, but it also significantly reduced the ESRD/dialysis risk without an episodic AKI or AKD risk. Clinical physicians should consider a personalized medicine approach by balancing GUTI episodes and cardiorenal outcomes for advanced CKD patients receiving SGLT2 inhibitors.

Using oral molecular hydrogen supplements to combat microinflammation in humans: a pilot observational study.

Background: Persistent inflammation over time can cause gradual harm to the body. Molecular hydrogen has the potential to specifically counteract reactive oxygen species (ROS), reduce disease severity, and enhance overall health. Investigations of the anti-inflammatory and antioxidant properties of oral solid hydrogen capsules (OSHCs) are currently limited, prompting our examination of the beneficial effects of OSHCs. Subsequently, we conducted a clinical study to assess the impact of OSHCs supplementation on individuals with chronic inflammation. Materials and methods: Initially, we evaluated the oxidative reduction potential (ORP) properties of the OSHCs solution by comparing it to hydrogen-rich water (HRW) and calcium hydride (CaH2) treated water. In our outpatient department, stable patients with chronic illnesses who were treated with varying doses of OSHCs were randomized into low-, medium-, and high-dose groups for 4 weeks. Primary outcomes included changes in the serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentrations after four weeks of OSHCs consumption. Secondary outcomes included changes in the Brief Fatigue Inventory-Taiwan (BFI-T) fatigue scale, Control Status Scale for Diabetes (CSSD70) scores, and Disease Activity Score 28 (DAS28). Results: Compared to HRW and CaH2, OSHCs demonstrated a prolonged reduction in ORP for 60 minutes in vitro and enabled a regulated release of hydrogen over 24 hours. A total of 30 participants, with 10 in each dosage (low/medium/high) group, completed the study. The average ESR120 significantly decreased from the first week to the fourth week, with a noticeable dose effect (low-dose group, p = 0.494; high-dose group, p = 0.016). Overall, the average CRP concentration showed a distinct decreasing trend after four weeks of OSHCs administration (w0 vs. w4, p = 0.077). The average DAS28 score demonstrated a significant decrease following OSHCs treatment. Furthermore, there were improvements in the BFI-T and CSSD70 scores. Conclusion: OSHCs supplementation may exert anti-inflammatory and antioxidant effects on individuals with chronic inflammation. However, further clinical studies could be investigated to explore the potential therapeutic effects of OSHCs.

Herlyn-Werner-Wunderlich Syndrome Complicated with Vesicovaginal Fistula: A Rare Case Report.

Herlyn-Werner-Wunderlich (HWW) syndrome is characterized by obstructed hemivagina and ipsilateral renal anomaly, a rare congenital anomaly of the genitourinary tract, resulting from malformations of the renal tract associated with Müllerian duct anomalies. The initial symptoms of HWW frequently present after menarche and may be nonspecific, leading to a delayed diagnosis. We presented a 19-year-old female with 3-year hematuria and abdominal pain. The final diagnosis of HWW syndrome with a rare vesicovaginal fistula was made. The treatment of HWW syndrome typically involves surgical intervention. The primary treatment is resection or removal of the obstructed vaginal septum. The patient underwent excision of vaginal septum and vaginal reconstruction via hysteroscopy, as well as repair of the vesicovaginal fistula. The patient improved well after surgery and fully recovered without sequelae after 3 months. In addition, unilateral renal agenesis is one of congenital abnormalities of the kidney and urinary tract, which are the most frequent cause of chronic kidney disease (CKD) in children. This report describes a patient of HWW syndrome with rarely combined vesicovaginal fistula, and highlights the importance of early recognition and management to prevent associated complications.

The impact of COVID-19 pandemic on air particulate matter exposure and heart attacks: a 5-year retrospective cohort study in Taiwan (2017-2021).

Background: Heart attacks including acute ST-segment elevation myocardial infarction (STEMI) and acute decompensated heart failure (ADHF) caused from the particulate matter (PM) and air pollutant exposures are positively associated with regional air pollution severity and individual exposure. The exceptional coronavirus disease epidemic of 2019 (COVID-19) may enhance the air conditions in areas under COVID-19 pandemic. We sought to study the impact of COVID-19 pandemic on air particulate matter (PM) exposure and heart attacks in Taiwan. Methods: This retrospective cohort study was conducted in one teaching hospital in Taichung, Taiwan. We examined emergency patients diagnosed with acute STEMI and ADHF from January 1, 2017, to March 31, 2020, (i.e., before the COVID-19 pandemic) and from April 1, 2020, to December 31, 2021, (after the COVID-19 pandemic). The effects of particulate matter with a diameter of less than 2.5 micrometers (PM2.5) and PM10 as well as temperature and humidity on environmental air pollutants were recorded. The analysis was performed with a unidirectional case-crossover research design and a conditional logistic regression model. Results: Both PM2.5 and PM10 levels had a positive association with the risk of acute STEMI before the COVID-19 pandemic (PM2.5 adjusted odds ratio (OR): 1.016, 95% confidence interval (CI): 1.003-1.032 and PM10 adjusted OR: 1.009, 95% CI: 1.001-1.018) and ADHF (PM2.5 adjusted OR: 1.046, 95% CI: 1.034-1.067 and PM10 adjusted OR: 1.023, 95% CI: 1.027-1.047). Moreover, the results demonstrated that PM2.5 and PM10 were not associated with the risk of acute STEMI or ADHF after the COVID-19 pandemic. Reduction in PM2.5 and PM10 levels after the COVID-19 pandemic were noted. Hospital admissions for acute STEMI (7.4 and 5.8/per month) and ADHF (9.7 and 8.2/per month) also decreased (21.6 and 15.5%) after the COVID-19 pandemic. Conclusion: In Taiwan, paradoxical reductions in PM2.5 and PM10 levels during the COVID-19 pandemic may decrease the number of hospital admissions for acute STEMI and ADHF. As the COVID-19 pandemic eases, the condition of air pollution may gradually become worse again. The governments should formulate better policies to improve the health of the public and the quality of the air.

Biomedical Evaluation of Early Chronic Kidney Disease in the Air Force: Building a Predictive Model from the Taiwan Military Health Service.

OBJECTIVE: Chronic kidney disease (CKD) is one of the most common diseases worldwide. The increasing prevalence and incidence of CKD have contributed to the critical problem of high medical costs. Due to stressful environments, aircrew members may have a high risk of renal dysfunction. A better strategy to prevent CKD progression in Air Force personnel would be to diagnosis CKD at an early stage. Since few studies have been conducted in Taiwan to examine the long-term trends in early CKD in Air Force aircrew members, this study is highly important. We investigated the prevalence of CKD and established a predictive model of disease variation among aircrew members. MATERIALS AND METHODS: In this retrospective study, we included all subjects who had received physical examinations at a military hospital from 2004 to 2010 and who could be tracked for four years. The Abbreviated Modification of Diet in Renal Disease Formula (aMDRD) was used to estimate the glomerular filtration rate (GFR) and was combined with the National Kidney Foundation/ Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) to identify CKD patients. RESULTS: A total of 212 aircrew members were assessed. The results showed that the prevalence of CKD was 3.8%, 9.4%, 9.0%, and 9.4% in each of the four years. According to the logistic regression analysis, abnormal urobilinogen levels, ketones, and white blood cell (WBC) counts in urine and a positive urine occult blood test increased the risk of CKD. A positive urine occult blood test can be used to predict the future risk of CKD. Moreover, the generalized estimating equation (GEE) model showed that a greater risk of CKD with increased examination time, age and seniority had a negative effect. In conclusion, abnormal urobilinogen levels, ketones, and urine WBC counts in urine as well as a positive urine occult blood test might serve as independent predictors for CKD. CONCLUSION: In the future, we can focus not only on annual physical examinations but also on simple and accurate examinations, such as urine occult blood testing, to determine the risk of CKD and prevent its progression in our aircrew members.

Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals.

BACKGROUND: Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. METHODS: This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. RESULTS: Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. CONCLUSION: SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

APOE-ε4 Alleles Modify the Decline of MMSE Scores Associated With Time-Dependent PM2.5 Exposure: Findings From a Community-Based Longitudinal Cohort Study.

OBJECTIVE: Limited research has explored the long-term effect of reduced PM2.5 exposure on cognitive function. This study aimed to investigate the effects of time-dependent PM2.5 exposure and the interactions of PM2.5 and aging on declines in Mini-Mental State Examination (MMSE) scores, in carriers and non-carriers of the APOE-ε4 allele. METHODS: Participants aged over 60 were recruited for this cohort study, undergoing MMSE tests twice from the Taiwan Biobank Program from 2008 to 2020. Participants with dementia or baseline MMSE scores <24 were excluded. Annual PM2.5 levels were estimated using a hybrid kriging/land use regression model with extreme gradient boosting, treated as a time-dependent variable. Generalized estimating equations were used to assess the impacts of repeated PM2.5 on MMSE decline, further stratified by the presence of APOE-ε4 alleles. RESULTS: After follow-up, 290 participants out of the overall 7,000 community residents in the Biobank dataset demonstrated incidences of MMSE declines (<24), with an average MMSE score decline of 1.11 per year. Participants with ε4/ε4 alleles in the APOE gene had significantly 3.68-fold risks of MMSE decline. High levels of PM2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. As annual levels of PM2.5 decreased over time, the impact of PM2.5 on MMSE decline also slowly diminished. CONCLUSION: Long-term PM2.5 exposure may be associated with increased risk of MMSE decline, despite improvements in ambient PM2.5 levels over time. Validation of these results necessitates a large-scale prospective cohort study with more concise cognitive screening tools.

MicroRNA regulators of vascular pathophysiology in chronic kidney disease.

Coronary artery disease (CAD) is a severe comorbidity in chronic kidney disease (CKD) due to heavy calcification in the medial layer and inflamed plaques. Chronic inflammation, endothelial dysfunction and vascular calcification are major contributors that lead to artherosclerosis in CKD. The lack of specific symptoms and signs of CAD and decreased accuracy of noninvasive diagnostic tools result in delayed diagnosis leading to increased mortality. MicroRNAs (miRNAs) are post-transcriptional regulators present in various biofluids throughout the body. In the circulation, miRNAs have been reported to be encapsulated in extracellular vesicles and serve as stable messengers for crosstalk among cells. miRNAs are involved in pathophysiologic mechanisms including CAD and can potentially be extended from basic research to clinical translational practice.

Evaluation of the safety and potential lipid-lowering effects of oral hydrogen-rich coral calcium (HRCC) capsules in patients with metabolic syndrome: a prospective case series study.

Background: Metabolic syndrome is characterized by a cluster-like occurrence of conditions such as hypertension, hyperglycaemia, elevated low-density lipoprotein (LDL) cholesterol or triglycerides (TG) and high visceral fat. Metabolic syndrome is linked to the build-up of plaque within the artery, which leads to disorders of the circulatory, nervous and immune systems. A variety of treatments target the regulation of these conditions; nevertheless, they remain dominant risk factors for the development of type 2 diabetes (T2DM) and cardiovascular disease (CVD), which affect 26.9% of the US population. Management and intervention strategies for improving cholesterol and/or TG are worthwhile, and recent studies on hydrogen treatment are promising, particularly as molecular hydrogen is easily ingested. This study aimed to investigate the lipid-lowering effects and quality of life (QOL) improvement of hydrogen-rich coral calcium (HRCC) in patients with metabolic syndrome. Methods: The patients, all Taiwanese, were randomly assigned to 3 different doses (low, medium, and high) of HRCC capsules. The primary outcome was the adverse effects/symptoms during this 4-week use of HRCC capsules. The secondary outcome was lipid profile changes. Complete blood count, inflammatory biomarkers, and QOL were also measured before and after the course of HRCC. Results: Sixteen patients with metabolic syndrome completed this study (7 males, 9 females; mean age: 62 years; range: 32-80). No obvious adverse effects were recorded. Only changes in blood TG reached significance. The baseline TG value was 193.19 µL (SD = 107.44), which decreased to 151.75 µL (SD = 45.27) after 4 weeks of HRCC (p = 0.04). QOL showed no significant changes. Conclusion: This study is the first human clinical trial evaluating HRCC capsules in patients with metabolic syndrome. Based on the safety and potential TG-lowering effects of short-term HRCC, further long-term investigations of HRCC are warranted. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05196295].

Enzalutamide Prior to Radium-223 Is Associated with Better Overall Survival in Metastatic Castration-Resistant Prostate Cancer Patients Compared to Abiraterone-A Retrospective Study.

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive stage of prostate cancer that often spreads to the bone. Radium-223, a bone-targeting radiopharmaceutical, has been shown to improve the overall survival in mCRPC in patients without visceral metastasis. However, the impact of prior systemic therapy on the treatment outcome of mCRPC patients receiving radium-223 remains unclear. This study aimed to investigate the optimal choice of systemic therapy before radium-223 in mCRPC patients. The study included 41 mCRPC patients who received radium-223 therapy, with 22 receiving prior enzalutamide and 19 receiving prior abiraterone. The results showed that the median overall survival was significantly longer in the enzalutamide group than in the abiraterone group (25.1 months vs. 14.8 months, p = 0.049). Moreover, the number of patients requiring blood transfusion was higher in the abiraterone group than in the enzalutamide group (9.1% vs. 26.3%, p = 0.16). The study also found that the number of doses of Radium-223 received was significantly associated with overall survival (≥5 vs. <5, HR 0.028, 95%CI 0.003-0.231, p = 0.001). Our study provides insights into the optimal treatment choice for mCRPC prior to radium-223, indicating that enzalutamide prior to radium-223 administration may have better outcomes compared to abiraterone in mCRPC patients without visceral metastasis.

Investigation of the underuse of adrenaline (epinephrine) and prognosis among patients with anaphylaxis at emergency department admission.

Background: Anaphylaxis is a potentially fatal condition; in severe cases of anaphylaxis, the cardiovascular system is often heavily involved. Adrenaline (epinephrine) is a cornerstone of the initial treatment of anaphylaxis. The use of epinephrine remains below expectations in clinical practice. Whether the underuse of epinephrine affects the prognosis of patients with anaphylaxis is still unclear. Materials and methods: This retrospective study included patients with anaphylaxis between 2011 and 2020 who were admitted to an emergency department (ED) in Taiwan. All patients were divided into two groups based on the use of epinephrine (or not), and we compared the demographic characteristics, allergens, clinical manifestations, management, and patient outcomes. Results: We reviewed the records of 314 subjects (216 males, 98 females; mean age: 52.78 ± 16.02 years) who visited our ED due to anaphylaxis; 107 (34.1%) and 207 (65.9%) patients were categorized into the epinephrine use group and the non-epinephrine use group, respectively. Arrival via ambulance (p = 0.019), hypotension (p = 0.002), airway compromise (p < 0.001) and altered consciousness (p < 0.001) were the deciding factors for epinephrine use among anaphylactic patients in the ED. The epinephrine use group had higher rates of other inotropic agent usage and fluid challenge. More than 90% of patients received bed rest, steroids, antihistamines, and monitoring. The epinephrine use group had a longer ED length of stay (387.64 ± 374.71 vs. 313.06 ± 238.99 min, p = 0.03) and a greater need of hospitalization. Among all severe symptoms, hypotension was the most tolerated decision factor for not using epinephrine. In this retrospective analysis, some patients with serious anaphylaxis did not experience adverse outcomes or death even without the use of epinephrine at ED admission. Emergent care focuses first on the airway, breathing, and circulation (ABC) and may compensate for the underusage of epinephrine. This could be the reason why epinephrine was underused among patients with anaphylaxis in the ED. Conclusion: In summary, early ABC management continues to play an important role in treating patients with severe anaphylaxis, even when epinephrine is not immediately available in clinical scenarios.

Caffeic acid phenethyl ester suppresses EGFR/FAK/Akt signaling, migration, and tumor growth of prostate cancer cells.

BACKGROUND: Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa. PURPOSE: We examined if caffeic acid phenethyl ester (CAPE) simultaneously suppresses the EGFR and Akt signaling, migration and tumor growth in PCa cells. METHODS: Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells. Western blot, immunoprecipitation, and immunohistochemistry staining were performed to determine the effects of CAPE on EGFR and Akt signaling. RESULTS: CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells. CAPE treatment inhibited the EGF-induced migration of PCa cells. Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells. Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts. CONCLUSIONS: Our study suggested that CAPE can simultaneously suppress the EGFR and Akt signaling in PCa cells and is a potential therapeutic agent for advanced PCa.

Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and the Incidence of Acute Kidney Injury in Taiwan.

Importance: The association between sodium-glucose transport protein 2 inhibitor (SGLT2i) use and the incidence of acute kidney injury (AKI) remains controversial. The benefits of SGLT2i use in patients to reduce AKI requiring dialysis (AKI-D) and concomitant diseases with AKI as well as improve AKI prognosis have not yet been established. Objective: To investigate the association between SGLT2i use and AKI incidence in patients with type 2 diabetes (T2D). Design, Setting, and Participants: This nationwide retrospective cohort study used the National Health Insurance Research Database in Taiwan. The study analyzed a propensity score-matched population of 104 462 patients with T2D treated with SGLT2is or dipeptidyl peptidase 4 inhibitors (DPP4is) between May 2016 and December 2018. All participants were followed up from the index date until the occurrence of outcomes of interest, death, or the end of the study, whichever was earliest. Analysis was conducted between October 15, 2021, and January 30, 2022. Main Outcomes and Measures: The primary outcome was the incidence of AKI and AKI-D during the study period. AKI was diagnosed using International Classification of Diseases diagnostic codes, and AKI-D was determined using the diagnostic codes and dialysis treatment during the same hospitalization. Conditional Cox proportional hazard models assessed the associations between SGLT2i use and the risks of AKI and AKI-D. The concomitant diseases with AKI and its 90-day prognosis, ie, the occurrence of advanced chronic kidney disease (CKD stage 4 and 5), end-stage kidney disease, or death, were considered when exploring the outcomes of SGLT2i use. Results: In a total of 104 462 patients, 46 065 (44.1%) were female patients, and the mean (SD) age was 58 (12) years. After a follow-up of approximately 2.50 years, 856 participants (0.8%) had AKI and 102 (<0.1%) had AKI-D. SGLT2i users had a 0.66-fold risk for AKI (95% CI, 0.57-0.75; P < .001) and 0.56-fold risk of AKI-D (95% CI, 0.37-0.84; P = .005) compared with DPP4i users. The numbers of patients with AKI with heart disease, sepsis, respiratory failure, and shock were 80 (22.73%), 83 (23.58%), 23 (6.53%), and 10 (2.84%), respectively. SGLT2i use was associated with lower risk of AKI with respiratory failure (hazard ratio [HR], 0.42; 95% CI, 0.26-0.69; P < .001) and shock (HR, 0.48; 95% CI, 0.23-0.99; P = .048) but not AKI with heart disease (HR, 0.79; 95% CI, 0.58-1.07; P = .13) and sepsis (HR, 0.77; 95% CI, 0.58-1.03; P = .08). The 90-day AKI prognosis for the risk of advanced CKD indicated a 6.53% (23 of 352 patients) lower incidence in SGLT2i users than in DPP4i users (P = .045). Conclusions and Relevance: The study findings suggest that patients with T2D who receive SGLT2i may have lower risk of AKI and AKI-D compared with those who receive DPP4i.

Investigation of Neurological Complications after COVID-19 Vaccination: Report of the Clinical Scenarios and Review of the Literature.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in 2019 and became a pandemic in 2020. Since then, vaccines have been approved to prevent severe illness. However, vaccines are associated with the risk of neurological complications ranging from mild to severe. Severe complications such as vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with acute ischaemic stroke have been reported as rare complications post-COVID-19 vaccination. During the pandemic era, VITT evaluation is needed in cases with a history of vaccination within the last month prior to the event. Cerebral venous sinus thrombosis (CVST) should be suspected in patients following immunization with persistent headaches who are unresponsive to analgesics. In this article, we investigated neurological complications after COVID-19 vaccination and provided more subsequent related clinical studies of accurate diagnosis, pathophysiological mechanisms, incidence, outcome, and management.

Case report: Hemophagocytic lymphohistiocytosis complicated by multiple organ dysfunction syndrome following aseptic encephalitis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening condition caused by excessive immune activation. Secondary HLH is usually triggered by infection, most often from viral infection or malignancy. Here, we present a case of secondary HLH, complicated by multiple organ dysfunction syndrome triggered by critical aseptic encephalitis. A 27-year-old man without any underlying disease presented to our hospital with fever, disturbance of consciousness, and generalized seizures. The patient was diagnosed with aseptic encephalitis with super-refractory status epilepticus. Although antiseizure medications and immunoglobulins were administered, the patient developed multiple organ dysfunction syndrome. HLH was later diagnosed based on hypertriglyceridemia, hyperferritinemia, splenomegaly, cytopenia, and phagocytosis of nucleated cells, as shown by a blood smear of bone marrow aspiration. Treatment with pulse steroid therapy and plasmapheresis was initiated rather than chemotherapy because of the patient's critical condition. However, the patient died of profound shock and multiple organ failure. Diagnosis of HLH is challenging in patients with severe infections because of similar clinical manifestations and laboratory findings. The early recognition of HLH provides patients with the opportunity to receive appropriate treatment, which can lead to increased survival and remission rates.

QSOFA and SOFA scores are valuable tools for predicting postoperative sepsis resulting from ureteroscopic lithotripsy (URSL).

The sequential organ failure assessment (SOFA) and quick sequential organ failure assessment (qSOFA) scores are new tools which are used to assess sepsis based on the Third International Consensus Definitions for Sepsis and Septic Shock Task Force. This study aimed to evaluate the feasibility of using the SOFA and qSOFA to predict post-ureteroscopic lithotripsy (URSL) sepsis. Patients who underwent URSL due to ureteral stone obstruction were retrospectively reviewed using SOFA and qSOFA scores. Patient characteristics including age, gender, comorbidities, American Society of Anesthesiologists Classification, stone burden, stone location, hydronephrosis status, infectious status, preoperative SOFA and qSOFA score were collected. Preoperative factors were analyzed to determine if they were correlated with postoperative sepsis. A total of 830 patients were included in this study, of whom 32 (3.9%) had postoperative sepsis. Multivariate analysis revealed that older age, proximal ureteral stones, severe hydronephrosis, and high preoperative qSOFA or SOFA score were significantly associated with postoperative sepsis. The areas under the curves of a qSOFA score ≥ 1 and SOFA score ≥ 2 for predicting postoperative sepsis were 0.754 and 0.823, respectively. Preoperative qSOFA and SOFA scores are convenient and effective for predicting post-URSL sepsis. Further preventive strategies should be performed in these high-risk patients.

Case report: Rhabdomyolysis and kidney injury in a statin-treated hypothyroid patient-kill two birds with one stone.

Statin treatment for hypercholesterolemia may cause reversible rhabdomyolysis and acute kidney injury in susceptible patients. However, persistent rhabdomyolysis and acute kidney injury following discontinuation of statins require careful evaluation of the underlying causes to avoid missing a curable disease. We describe a 50-year-old woman with hypercholesterolemia [total cholesterol 345 mg/dl, low-density lipoprotein cholesterol (LDL-C) 266 mg/dL] on atorvastatin therapy (40 mg daily) for 1 month that presented with myalgia and muscle weakness. Relevant laboratory studies revealed persistent higher hypercholesterolemia with total cholesterol (312 mg/dL), high creatine kinase (CK) (5,178 U/L), and high creatinine levels (1.5 mg/dL) without dysmorphic red blood cells and proteinuria. Despite the cessation of statin therapy, serum CK level increased to 9,594 U/L, and creatinine remained at 1.5 mg/dL. A thorough work-up to assess potential underlying causes indicated low T3 and free T4 and high thyroid-stimulating hormone (TSH) levels, consistent with hypothyroidism. With aggressive thyroxine replacement for 1 month, all of the clinical features, along with elevated serum CK and creatinine levels, were completely resolved. This case highlights the fact that hypothyroidism must be kept in mind as a potential cause of concomitant myopathy and kidney injury, especially in patients with statin-resistant hypercholesterolemia.

From Bench to Bedside: Clinical and Biomedical Investigations on Hepatitis C Virus (HCV) Genotypes and Risk Factors for Albuminuria.

An extrahepatic manifestation of nephropathies can be a feature of the chronic hepatitis C virus (HCV) infection. Albuminuria is a major risk factor for nephropathies and chronic kidney disease (CKD). The correlation between HCV genotypes and albuminuria is still unclear. In this study, investigations have been done for the biomedical tools and methodologies used in the National Health and Nutrition Examination Survey (NHANES) public database. We searched the 2007−2016 NHANES public database to retrieve data regarding the different HCV genotypes and clinical scenarios. This study attempted to investigate the impacts of HCV genetic diversity, associated comorbidities, and racial differences on albuminuria. The urine albumin/creatinine ratio (ACR) was the primary endpoint. Among 40,856 participants, 336 participants with positive and 237 with negative HCV RNA tests were analyzed, excluding 14,454 participants with negative HCV antibodies and 25,828 which were missed. After controlling for sex, race, education level, smoking, diabetes mellitus, hepatitis B, alcohol use, and body mass index (BMI) with a generalized linear equation, HCV genotype 2 was more likely than any other genotype to cause albuminuria based on the urine ACR (p < 0.001). The generalized linear equation also demonstrated a significantly higher urine ACR, including hepatitis B (p < 0.001), diabetes mellitus (p < 0.001), and smoking (p = 0.026). In summary, the patients with HCV genotype 2 presented with increased albuminuria in comparison with other HCV genotypes in this 10-year retrospective analysis. HCV infection could be a risk factor of CKD; early diagnosis and appropriate treatment may improve clinical outcomes.

Delayed Skin Reactions to COVID-19 mRNA-1273 Vaccine: Case Report and Literature Review.

BACKGROUND: The COVID-19 mRNA vaccine was granted emergency use authorization (EUA) on December 18, 2020. Some patients experienced a transient, pruritic rash at the injection site, which was referred to as "COVID arm". It is considered a delayed-type hypersensitivity reaction and occurs mostly in individuals after vaccination with the Moderna vaccine but rarely with other mRNA vaccines. CASE SUMMARY: A healthy 33-year-old woman with no history of disease or long-term medication presented with fever and rash on the left upper arm three days after her first vaccination with the mRNA-1273 vaccine (Moderna). RESULTS: After treatment with antihistamines, all lesions gradually resolved over the following 4 to 5 days. CONCLUSION: We report a case of "COVID arm": a localized erythematous rash surrounding the injection site that arose three days after the first dose of the Moderna COVID-19 vaccine. Delayed injection site reactions occurred in approximately 0.8% of vaccinated people after the first dose and in approximately 0.2% after the second dose. The lesions persisted for several days and then resolved without treatment. Health care providers were not prepared to address these delayed local reactions to the mRNA-1273 vaccine. Given the scale-up of mass vaccination campaigns worldwide, these skin reactions may likely generate concerns among patients and requests for evaluation. Although these skin reactions have not been consistently recognized, guidance regarding the second dose of the vaccine has varied, and many patients have unnecessarily received antibiotic agents.