Clinical Course Research Articles

A Primary Health Care Program and COVID-19. Impact in Hospital Admissions and Mortality.

Most patients with mild or moderate COVID infection did not require hospital admission, but depending on their personal history, they needed medical supervision. In monitoring these patients in primary care, the design of specific surveillance programs was of great help. Between February 2021 and March 2022, EDCO program was designed in Tenerife, Spain, to telemonitor patients with COVID infection who had at least one vulnerability factor to reduce hospital admissions and mortality. The aim of this study is to describe the clinical course of patients included in the EDCO program and to analyze which factors were associated with a higher probability of hospital admission and mortality. Retrospective cohort study. We included 3848 patients with a COVID-19 infection age over 60years old or age over 18years and at least one vulnerability factor previously reported in medical history. Primary outcome was to assess risk of admission or mortality. 278 (7.2%) patients required hospital admission. Relative risks (RR) of hospital admission were oxygen saturation ≤ 92% (RR: 90.91 (58.82-142.86)), respiratory rate ≥ 22 breaths per minute (RR: 20.41 (1.19-34.48), obesity (RR: 1.53 (1.12-2.10), chronic kidney disease (RR:2.31 (1.23-4.35), ≥ 60years of age (RR: 1.44 (1.04-1.99). Mortality rate was 0.7% (27 patients). Relative risks of mortality were respiratory rate ≥ 22 breaths per minute (RR: 24.85 (11.15-55.38), patients with three or more vulnerability factors (RR: 4.10 (1.62-10.38), oxygen saturation ≤ 92% (RR: 4.69 (1.70-15.15), chronic respiratory disease (RR: 3.32 (1.43-7.69) and active malignancy (RR: 4.00 (1.42-11.23). Vulnerable patients followed by a primary care programme had admission rates of 7.2% and mortality rates of 0.7%. Supervision of vulnerable patients by a Primary Care team was effective in the follow-up of these patients with complete resolution of symptoms in 91.7% of the cases.

Clinical characteristics and outcomes after trigeminal schwannoma resection: a multi-institutional experience.

Given their rarity, the clinical course of patients undergoing trigeminal schwannoma (TS) resection remains understudied. The objective of this study is to describe clinical characteristics and outcomes in patients undergoing surgical resection for TS in a multi-institutional cohort. This is a retrospective study of patients undergoing TS resection at two institutions between 2004 and 2022. Patient, radiographic, and clinical characteristics were reviewed and analyzed with standard statistical methods. Thirty patients were included. The median patient age was 43 (IQR: 35-52) years, and 14 (47%) patients were female. Median clinical and radiographic follow-ups were 43 (IQR: 20-81) and 47 (IQR: 27-97) months respectively. The most common presenting symptoms were trigeminal hypesthesia (57%) and headaches (30%), diplopia (30%), and ataxia/cerebellar signs (30%). The median maximum tumor diameter was 3.3 (IQR: 2.5-5.4) cm. Most tumors were Samii type C (50%) and mixed cystic-solid (63%). Surgical approaches included endoscopic endonasal (33%), supratentorial (30%), combined/staged (20%), infratentorial (10%), and anterior petrosal (7%) approaches. Gross-total resection was achieved in 16 (53%) patients. Radiographic tumor recurrence was noted in four patients at a median of 79 (range 5-152) months. Twenty-six (87%) patients reported improvements in at least one symptom by last follow-up. The most common perioperative complication was new cranial nerve deficit, with 17% of patients having a transient deficit and 10% having a permanent cranial nerve deficit. Surgical resection of TS showed good progression-free survival and symptom improvement, but was associated with cranial nerve deficits.

Children and young adults with newly diagnosed rhabdomyosarcoma metastatic to bone treated on Children's Oncology Group studies.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Despite bone metastases being present in 5% of patients at diagnosis, there are limited studies examining these outcomes. We sought to define the prognostic factors, clinical courses, and outcomes of children treated on Children's Oncology Group (COG) clinical trials with RMS metastatic to bone at diagnosis. We performed a retrospective analysis of patients diagnosed with bone metastatic RMS enrolled on COG RMS clinical trials (D9802, D9803, ARST0431, or ARST08P1) between 1997 and 2013. RMS metastatic to bone was identified in 154 patients at a median age of 14.9years at diagnosis. Fifty-eight percent of patients were male, 90% had metastases at additional sites, 74% had alveolar histology, and extremity was the most common primary site (31%). Eighty-six percent of patients (n=133) received radiation therapy. The 3- and 5-year event-free survival (EFS) was 15.4% and 14.5%, respectively. The 3- and 5-year overall survival (OS) was 30.4% and 18.0%, respectively. We identified alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation as poor prognostic characteristics for both EFS and OS in univariate analysis. Lack of radiation was not significant when excluding patients with events prior to 20weeks. This study is the largest analysis of patients with bone metastatic RMS, and defines the poor overall outcomes and negative prognostic factors for these patients. They may be eligible for therapy deintensification for improved quality of life or pursuit of novel treatments/approaches, which are desperately needed.

Association of Glutathione Transferase M1, T1, P1 and A1 Gene Polymorphism and Susceptibility to IgA Vasculitis

Endothelial cell injury is a hallmark of IgA vasculitis (IgAV), possibly associated with various factors, including oxidative stress. Certain single nucleotide polymorphisms (SNPs) of glutathione S-transferases (GST) genes have been shown to increase susceptibility to oxidative stress. The objective of our study was to evaluate the gene polymorphisms of GSTM1, GSTT1, GSTP1, and GSTA1 in patients with IgAV. DNA was extracted from the blood of 124 children with IgAV and 168 age-matched healthy controls. A higher frequency of the GSTM1 null genotype was observed in patients with gastrointestinal (GI) system involvement compared to those without GI system involvement (51.5% vs. 28.6%, p = 0.011). Additionally, the GSTM1 null genotype was less prevalent (30.8% vs. 69.2%, p = 0.032), while the GSTP1 Val/Val genotype was significantly more prevalent in patients who developed urogenital complications (scrotal swelling) during the course of the disease (60% vs. 40%, p = 0.039). This study is the first to suggest an association between GSTM1 and GSTP1 polymorphisms and various phenotypes observed during the clinical course of IgAV in the pediatric population. However, it was performed on a national and likely single ethnic cohort, too small for definitive conclusions, so larger studies are needed to confirm this association.

American registry of ambulatory and acute decompensated heart failure (AMERICCAASS registry): Rationale and design.

Heart failure (HF) is a highly prevalent and progressive condition associated with significant morbidity and mortality rates. Acute decompensated HF precipitates millions of hospitalizations each year. Despite therapeutic advances, the overall prognosis of HF is poor. The varying clinical courses and outcomes of patients with this disease may be due to region-specific gaps and since most HF studies are conducted in developed countries, the participation of Latin American and Caribbean countries is low. Considering this, the American Registry of Ambulatory and Acute Decompensated Heart Failure (AMERICCAASS) aims to characterize the population with ambulatory and acute decompensated HF in the American continent and to determine rehospitalization and survival outcomes during the 12months of follow-up. AMERICCAASS Registry is an observational, prospective, and hospital-based registry recruiting patients with ambulatory or acute decompensated HF. The registry plans to include between two and four institutions per country from at least 20 countries in the Americas, and at least 60 patients recruited from each participant institution regardless of their ambulatory or acutely decompensated condition. Ambulatory patients with confirmed HF diagnosis or inpatients presenting with acute decompensated HF will be included. Follow-up will be performed at 12months in ambulatory patients or 1, 6, and 12months after hospital discharge in acutely decompensated HF patients. This ongoing study began on 1 April 2022, with recruitment scheduled to end on 30 November 2023, and follow-up on 31 January 2025. Ethics approval was obtained from the Biomedical Research Ethics Committee of Fundación Valle del Lili. Data collected in the AMERICCAASS registry is being stored on the electronic platform REDCap (Research Electronic Data Capture), which allows different forms for patient groups to enable unbiased analyses. For quantitative variables comparison, we will use the Student's t-test or non-parametric tests accordingly. Categorical variables will be presented as proportions, and groups will be compared with Fisher's exact test. The significance level will be <0.05 for comparisons. Readmissions and post-discharge mortality will be calculated as proportions at 1, 6, and 12months, with a survival analysis by conditional probability and the Kaplan-Meier method. AMERICCAASS Registry is intended to be the most important registry of the continent for obtaining important information about demographics, aetiology, co-morbidities, and treatment received, either ambulatory or hospitalized. This registry may contribute to the optimization of national and regional evidence and public policies for the diagnosis and treatment of HF disease.

Anti-inflammatory response to 1,8-Cineol and associated microbial communities in Otitis media patients

Chronic Otitis Media (COM) is defined as long term inflammation and colonization with pathogenic bacteria due to a defect or retraction of the tympanic membrane. Surgical interventions are often augmented by antibiotic resistance development and therefore, off-label treatment using the natural drug 1,8-Cineol was carried out. All COM patients underwent antibiotic therapy and middle ear surgery and developed antibiotic resistances. Microbiological investigations from the auditory canal and stool samples were performed in correlation with the clinical course. Therapy of COM patients with 1,8-Cineol revealed a clear reduction of inflammatory microbes P. aeruginosa and Proteus mirabilis in ear samples as well as intestinal Prevotella copri, which was associated with an improved clinical outcome in certain individuals. The present off-label study revealed manifold anti-inflammatory effects of the natural monoterpene 1,8-Cineol in Otitis media patients. A better understanding of the underlying mechanisms will improve the current treatment options and possible forms of application of this natural drug.

Case report of pharmacokinetic analysis of continuous intravenous infusion of fentanyl in a patient with severe burn: burn shock stage complicates pain management

BackgroundFentanyl is widely used as an analgesic and sedative for patients with severe burn injuries in intensive care units. However, pharmacokinetic (PK) data for fentanyl, particularly for continuous intravenous infusion during the acute phase of burn injuries, are limited. Here, we report the clinical course and changes in blood fentanyl concentrations during the acute phase in a patient with severe burns treated with continuous intravenous infusion of fentanyl.Case presentationA woman in her 40s, with burns caused by a gas cylinder explosion, was transported to our hospital. The patient had burn wounds on face, neck, shoulders, and all four extremities, with a total burn area of 39.0%. For pain relief, the patient received a continuous infusion of 0.01 mg/mL fentanyl (20–30 µg/h) with a target blood concentration of 1.0–1.5 ng/mL, but continued to suffer from pain due to burning during the acute phase. We measured the blood fentanyl concentrations and found that all concentrations obtained during the acute phase were subtherapeutic. Notably, during the burn shock stage, blood concentrations of fentanyl were 0.50 ng/mL on day 1 and 0.66 ng/mL on day 2, indicating that the blood concentration did not rise sufficiently for the dosage. From days 0 to 2, the patient was administered a massive fluid load for burn shock. After the burn shock stage resolved, fentanyl concentrations gradually approached the target range, and the pain rating scale improved, even though the fentanyl administration rate remained unchanged (30 µg/h).ConclusionsMajor changes in the fluid volumes of body compartments that occur with large burns might increase the volume of fentanyl distribution, thereby lowering its concentration when a standard dose is administered. Our findings indicate that the PK of fentanyl in patients with severe burns can be substantially affected, especially during the shock phase, implying the importance of titrating analgesics for clinical efficacy in the acute phase.

Clinical characteristics and outcomes of pediatric patients with autoimmune gastritis.

Autoimmune gastritis (AIG) is a rare chronic inflammatory disorder with potential long-term sequelae including gastric neoplasia. There is limited data on the natural history of pediatric AIG. We aimed to characterize the clinical course and outcomes of children with AIG. This was a multicenter retrospective study that included pediatric patients diagnosed with AIG between January 1, 2000 and December 31, 2021. Diagnosis of AIG was based on the demonstration of histological corpus-predominant atrophic gastritis, with or without positive antiparietal cell (APCA) or anti-intrinsic factor (IF) antibodies. Demographic, clinical, laboratory, endoscopic, and histologic data were retrieved, along with follow-up data. Thirty-three patients, (23 females, [69.7%], median age 12.0 [interquartile range 7.0-15.0] years at diagnosis) were identified. Twenty-two patients (66.7%) had positive APCA and/or anti-IF serology. The most common presenting manifestation was iron deficiency anemia (75%), and accompanying autoimmune disorders were significantly more common in patients with positive serology (62% vs. 18%, p < 0.05). Pseudo-pyloric or intestinal-type metaplasia was present at diagnosis in eightpatients (24%), and 11 additional patients (33%) developed metaplasia during a median follow-up time of 27 (17.5-48.3) months. One patient developed a type 1 gastric neuroendocrine tumor.Helicobacter pyloriwas identified in only one patient, while two patients had prior eradication. Endoscopic and histologic improvements weren't identified in any patients. AIG should be considered in patients with autoimmunity and resistant iron-deficiency anemia. H. pylori infection may not be associated with pediatric AIG. The development of neuroendocrine tumor in one patient, and the high rates of metaplasia, highlight the importance of surveillance.

Outcomes of myocarditis in systemic sclerosis: A 3-year follow-up.

The clinical course, the outcomes of myocarditis, and the imaging progression of cardiac magnetic resonance imaging (MRI) in systemic sclerosis (SSc) are still unknown. We aimed at defining changes in cardiac MRI findings, the clinical course, and the outcomes of SSc patients previously defined as having myocarditis by cardiac MRI. Methods: This prospective cohort study included SSc patients, who had previously been diagnosed with myocarditis through cardiac MRI at the Scleroderma Clinic of Khon Kaen University, between 2018 and 2020 and had had annual follow-ups of cardiac MRI for at least 3 years. Data on demographics, clinical characteristics, cardiac MRI findings, treatment regimens, and outcomes were collected. Serial cardiac MRI on a yearly basis was analyzed to assess changes in myocardial involvement over the 3-year period. Ten SSc patients diagnosed with myocarditis via cardiac MRI were included. Most belonged to the diffuse cutaneous subset with a mean age of 58.3±8.6 years and were mildly symptomatic. Initial cardiac MRI findings showed myocardial edema and hyperemia in all patients and eight patients had had pre-existing myocardial scars, suggesting disease chronicity. Treatment for concomitant interstitial lung disease involved steroids with either cyclophosphamide or mycophenolate mofetil in 6 patients. Outcomes of myocarditis were stable, improving, and worsening in 4, 4, and 2 patients, respectively. There was no complete resolution of the cardiac MRI indices for myocarditis, and none had had major cardiac events. Although SSc myocarditis on cardiac MRI may improve or show stability, the changes remained persistent. Among patients with SSc and mildly symptomatic myocarditis, the efficacy of steroids and immunosuppressive therapy is inconclusive. Over a 3-year follow-up, the prognosis had been acceptably good with no cardiac events.

Clinical courses and predictors of left ventricular systolic dysfunction in systemic sclerosis: A cohort study.

Left ventricular systolic dysfunction (LVSD) is a cardiac involvement that is the leading cause of death among patients with systemic sclerosis (SSc). We aimed to define the clinical course and predictors of LVSD among SSc patients. We conducted a cohort study among adult patients with SSc who were followed up from 2013 to 2020. Semiparametric Cox regression analysis with robust clustering by cohort identification number was used to evaluate the predictors of LVSD. Among the 3, 987 person-years, LVSD was defined in 35 of 419 SSc patients for an incidence of 0.88 per 100 person-years. The median duration of the disease was 8.5 (interquartile range (IQR) 4.9-12.9) years. Every 1-point increase in the modified Rodnan skin score (mRSS) and salt and pepper skin were strong predictors of LVSD, with a respective adjusted hazard ratio (HR) of 1.05 and 3.17. During follow-up, 26 cases (74.3%) had unimproved LVSD. The strong predictors of the unimprovement of LVSD were every 1-point increase in mRSS (HR 1.05), every 1 mg increase in prednisolone treatment (HR 1.05), and every 1 U/L increase in creatine kinase (CK) (HR 1.001). Mycophenolate treatment was a protective factor against the unimprovement of LVSD in SSc (HR 0.15). LVSD was frequently found in patients with diffuse cutaneous SSc, and in most cases, it remained unimproved during follow-up. High mRSS, steroid use, and high CK levels were predictors of unimproved LVSD, whereas mycophenolate treatment might prevent the progression of LVSD. Steroids should be prescribed with caution in patients with longer disease duration.

Outcomes of Covid-19 Vaccine-Associated Glomerular Diseases (CVAGD) – A Case Series from India

Background Several cases of glomerular diseases following Covid-19 vaccination, especially mRNA vaccines, have been reported. However, there is little data on glomerular diseases associated with the two vaccines widely available in India (Covaxin and Covishield) and their long-term outcomes. Materials and Methods This was a prospective observational study conducted between May 2021 and May 2023. Patients with new-onset or relapse of proteinuria, hematuria, or renal failure within 30 days of Covid-19 vaccination were included. Data on pre-existing renal disease, vaccine type, symptomatology, laboratory reports, kidney biopsy findings, and treatment details were collected. The clinical course and long-term renal outcomes were studied. Results Sixteen patients with Covid-19 vaccine associated glomerular disease (CVAGD) were studied. The median age was 28 years (IQR 20.5–40) and median time of symptom onset was 14 days (IQR 10–16.5) after vaccination. Renal syndromes at presentation were nephrotic syndrome in seven patients (43.75%), nephritic syndrome in seven patients (43.75%), and rapidly progressive renal failure in two patients (12.5%). Kidney biopsy revealed minimal change disease in five patients (31.2%); IgA nephropathy in four patients (25%); C3 glomerulopathy, lupus nephritis, and focal segmental glomerulosclerosis in two patients each (12.5%); and pauci-immune glomerulonephritis (ANCA-associated vasculitis) in one patient (6.25%). Eleven patients were treated with immunosuppressive drugs. Median duration of follow-up was 20 months (IQR 18–21). At last follow-up, 11 patients had complete recovery of renal failure and proteinuria and 4 patients had partial recovery. Conclusion The most common lesions in this series were minimal change disease and IgA nephropathy. The overall long-term outcome of CVAGD appears good.

Nonadherence to oral cancer chemotherapy in hepatocellular carcinoma: prevalence and predictive factors in Vietnam

PurposeStandard oral cancer chemotherapy (OCT) or targeted therapy (OTT) has expanded the treatment methods for hepatocellular carcinoma (HCC). However, its principal nonadherence causes a reduction in efficacy. We aimed to evaluate the status of nonadherence and influencing factors among outpatient patients with HCC.Patients and methodsIn 2021, a prospective observational study was conducted on 384 patients with either old or newly diagnosed HCC treated with OTT. Nonadherence to OCT was determined using the eight-item Morisky Medication Adherence Scale, with a score < 6 points. The patients were finished with a six-month follow-up investigation by questionnaires.Results54,8% of HCC outpatients were nonadherent to OCT, with a mean Morisky score of 5.19. They dropped out of the treatment mainly because of drug side effects, such as fatigue (72.4%), hand-foot syndrome (42.7%), diarrhea (38.3%), nausea (25%), insomnia (24.7%), abdominal pain (12%), and anxiety about these adverse events (65.9%). Additionally, financial difficulties and low relative copayments were significantly correlated with the noncompliant treatment of patients (OR = 2.29, 95% CI = 1.32–3.98, P = 0.003; OR = 4.36, 95% CI = 0.95–19.93, P = 0.039, respectively). Moreover, inadequate individual information about the clinical course, the art of treatment, and medication usage instructions were suggestive barriers to adherence to treatment (OR = 1.96, 95% CI = 1.08–3.55, P = 0.024; OR = 1.86, 95% CI = 1.1–3.14, P = 0.02; OR = 2.34, 95% CI = 1.29–4.26, P = 0.004, respectively). Finally, a low level of trust in doctors was an essential factor in nonadherence (Mean of the Anderson Trust in Physician Scale scores counted 38.12 vs. 43.97, respectively for non-adherence vs. adherence, P = 0.00001).ConclusionsThis study suggests a high rate of primary nonadherence to standard oral targeted therapy among HCC outpatient patients because of drug side effects, patient awareness of treatment, and lack of confidence in healthcare providers. Close supervision, proper medication instructions, appropriate dosage reductions, and comprehensive patient counseling might be necessary to control nonadherence.

Pyruvate dehydrogenase deficiency in a young boy: a clinical case

BACKGROUND: Pyruvate dehydrogenase deficit is a severe hereditary mitochondrial metabolic disease characterized by impaired energy metabolism and manifested by a wide range of neurological symptoms. The difficulty in selecting therapy is due to insufficient data on the management of children with this pathology owing to death at an early age and insufficient diagnosis during life. The accurate prevalence of the disease is unknown, presumably 1 in 1,000,000, which makes it attributable to orphan diseases. CLINICAL CASE DESCRIPTION: This article presents a case of a child with a rare neurometabolic disease pyruvate dehydrogenase complex E1 deficiency. The diagnosis was suspected after his birth based on neurological symptoms, neonatal hyperammonemia, and hyperlactatemia and confirmed after exome sequencing, where a homozygous variant of the nucleotide sequence in the PDNA1 gene (X-19359612-C-E) was determined. At the age of 2 months, he began to receive a ketogenic diet — a high-fat, low-carbohydrate dry mixture for enteral nutrition, metabolic therapy, and Vit B1 (300 mg/day). The article presents indicators of biochemical blood testing, acid-base state of blood, and dynamics of the neurological picture during the period of observation of the patient. CONCLUSION: Early diagnosis and initiation of therapy is crucial for the physical and neuropsychiatric development of children with this pathology. Despite the lack of highly effective etiotropic treatment, in some cases, an improvement in the clinical course is observed with the use of thiamine preparations and adherence to a ketogenic diet.

Prevalence and characteristics of the 'bad feeling' among healthcare professionals in the context of emergency situations: A Bi-Hospital Survey.

Clinical decision-making is based on objective and subjective criteria, including healthcare workers impressions and feelings. This research examines the perception and implications of a 'bad feeling' experienced by healthcare professionals, focusing on its prevalence and characteristics. A cross-sectional paper-based survey was conducted from January to July 2023 at the University Medicine Greifswald and the hospital Sömmerda involving physicians, nurses, medical students and trainees from various specialties. With ethics committee approval, participants were recruited and surveyed at regular clinical events. Data analysis was performed using SPSS® Statistics. The manuscript was written using the Strobe checklist. Out of 250 questionnaires distributed, 217 were valid for analysis after a 94.9% return rate and subsequent exclusions. Sixty-five per cent of respondents experience the 'bad feeling' occasionally to frequently. There was a significant positive correlation between the frequency of 'bad feeling' and work experience. The predominant cause of this feeling was identified as intuition, reported by 79.8% of participants, with 80% finding it often helpful in their clinical judgement. Notably, in 16.1% of cases, the 'bad feeling' escalated in the further clinical course into an actual emergency. Furthermore, 60% of respondents indicated that this feeling occasionally or often serves as an early indicator of a potential, yet unrecognised, emergency in patient care. This study demonstrates the relevance of clinical experience to decision-making. As an expression of this, there is a correlation between the frequency of a 'bad feeling' and the number of years of experience. It is recommended that the 'bad feeling' be deliberately acknowledged and reinforced as an early warning signal for emergency situations, given its significant implications for patient safety. Future initiatives could include advanced training and research, as well as tools such as pocket maps, to better equip healthcare professionals in responding to this intuition.

The relationship between Nuclear Factor-Kappa B and Inhibitor-Kappa B parameters with clinical course in COVID-19 patients.

We aimed to investigate the serum Nuclear Factor Kappa B (NF-κB) p105, NF-κB p65 and Inhibitor Kappa B Alpha (IκBα) levels in patients with mild/moderate Coronavirus Disease 2019 (COVID-19) and their association with the course of the disease. Blood was drawn from 35 COVID-19 patients who applied to the Department of Emergency Medicine of Istanbul University-Cerrahpasa at the time of diagnosis and from 35 healthy individuals. The patients were evaluated to have mild/moderate degree of disease according to National Early Warning Score 2 (NEWS2) scoring and computed tomography (CT) findings. The markers were studied in the obtained serum samples, using enzyme-linked immunoassay (ELISA). Receiver Operating Characteristic (ROC) analysis was performed. Statistical significance was evaluated to be p < 0.05. NF-κB p105 levels were significantly higher in the COVID-19 group compared to the control group. C-reactive protein (CRP), D-dimer, ferritin levels of the patients were significantly higher (p < 0.001) compared to the control group, while the lymphocyte count was found lower (p = 0.001). IκBα and NF-κB p65 levels are similar in both groups. Threshold value for NF-κB p105 was above 0.78 ng/mL, sensitivity was 71.4% and specificity was 97.1% (p < 0.05). NF-κB p105 levels at the time of diagnosis of the patients who required supplemental oxygen (O2), were significantly higher (p < 0.01). The rise in serum NF-κB p105 levels during the early stages of infection holds diagnostic value. Besides its relation with severity might have a prognostic feature to foresee the requirement for supplemental O2 that occurs during hospitalization.

Outcomes of patients with alcohol-associated hepatitis and acute kidney injury - Results from the HRS Harmony Consortium.

The development of acute kidney injury (AKI) in the setting of alcohol-associated hepatitis (AH) portends a poor prognosis. Whether the presence of AH itself drives worse outcomes in patients with cirrhosis and AKI is unknown. Retrospective cohort study of 11 hospital networks of consecutive adult patients admitted in 2019 with cirrhosis and AKI. AKI phenotypes, clinical course, and outcomes were compared between AH and non-AH groups. A total of 2062 patients were included, of which 303 (15%) had AH, as defined by National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria. Patients with AH, compared to those without, were younger and had higher Model for End-stage Liver Disease-Sodium (MELD-Na) scores on admission. AKI phenotypes significantly differed between groups (p < 0.001) with acute tubular necrosis occurring more frequently in patients with AH. Patients with AH reached more severe peak AKI stage, required more renal replacement therapy, and had higher 90-day cumulative incidence of death (45% [95% CI: 39%-51%] vs. 38% [95% CI: 35%-40%], p = 0.026). Using no AH as reference, the unadjusted sHR for 90-day mortality was higher for AH (sHR: 1.24 [95% CI: 1.03-1.50], p = 0.024), but was not significant when adjusting for MELD-Na, age and sex. However, in patients with hepatorenal syndrome, AH was an independent predictor of 90-day mortality (sHR: 1.82 [95% CI: 1.16-2.86], p = 0.009). Hospitalised patients with cirrhosis and AKI presenting with AH had higher 90-day mortality than those without AH, but this may have been driven by higher MELD-Na rather than AH itself. However, in patients with hepatorenal syndrome, AH was an independent predictor of mortality.

Nationwide incidence of and risk factors for undergoing incisional glaucoma surgery following infantile cataract surgery

Nationwide incidence and risk factors for incisional glaucoma surgery post-infantile cataract (IC) surgery in children remain poorly understood. We conducted a population-based cohort study using the Korean national health claims database to identify IC patients diagnosed before age 1 who had IC surgery among all Korean born between 2008 and 2018 (n = 9,593,003). We estimated the annual occurrence of undergoing incisional glaucoma surgery following IC surgery in the general population aged 0–10. The risk factors for incisional surgery including systemic comorbidities and ophthalmic anomalies were analyzed by multivariable logistic regression. Of 650 patients who had undergone IC surgery with a mean (standard deviation [SD]) follow-up period of 6.2 (3.2) years, 92 (14.2%) were diagnosed with glaucoma following infantile cataract surgery (GFICS). Among them, 21 patients (22.8%) underwent incisional glaucoma surgery after a mean (SD) follow-up duration of 5.4 (2.8) years from the diagnosis of GFICS. Median (InterQuartile Range) age at incisional surgery was 4 (2,6) years old. Twenty of 21 patients (95.2%) underwent incisional glaucoma surgery within 3 years of diagnosis of GFICS. No factors, except younger age at glaucoma diagnosis (P = 0.03), were associated with undergoing incisional surgery. These findings can better understand the epidemiologic features and clinical courses of GFICS.

Analysis of BK Virus Infection in Children After Hematopoietic Cell Transplantation: A Retrospective Single-Center Study.

BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Viruses can be found in urine and serum of immunocompromised patients. This study aimed to evaluate the incidence, clinical course, and risk factors for BKV infection in children undergoing HSCT. Retrospectively analyzed children who underwent HSCT at Beijing Children's Hospital, Capital Medical University from June 2020 to June 2022. Data related to the clinical manifestations, engraftment, and prognosis were extracted from medical records. Patients were divided into the case group and the control group, according to the BKV infection or not after HSCT. A total of 149 patients were enrolled in this study, and 61 (40.9%) patients developed BKV infection after HSCT. Among the 61 patients, BKV load was detected in all patients in urine samples and 22 patients in blood samples. The median value of BKV DNA copies in urine and plasma were 9.50×107 (5.37×102 to 6.84×109) copies/mL and 2.97×103 (9.96×102 to 3.58×108) copies/mL, respectively. The median time from beginning of the conditioning regimen to BKV infection was 23 (0 to 273) days, and the first positive time of urinary BKV was earlier than that of blood (13.5d [0.0 to 123.0d] vs. 30.5d [7.0 to 165.0d], P=0.003). Among the patients with BKV infection, 36 (59.0%) patients met the diagnosis of hemorrhagic cystitis (HC), and the incidence was higher than that in the control group (P<0.001). Similarly, 15 (24.6%) patients developed renal function damage in the case group and the proportion was higher than that in the control group. The median follow-up was 5.67 (0.03 to 24.90) months, and there was no significant difference in 1-year overall survival rate between the case group and the control group (84.2%±5.7% vs. 95.3%±2.3%, P=0.688), but the incidence of TA-TMA/VOD (31.1%) and diffuse alveolar hemorrhage (9.8%) in the case group was higher than that in the control group (P=0.002 and 0.038, respectively). Multivariate analysis showed that age above 5 years old (OR=9.039, 95% CI: 3.561-24.333, P<0.001) and use of MMF (OR=2.708, 95% CI: 1.041-7.044, P<0.05) were independent risk factors for BKV infection after HSCT. Among children after HSCT, the incidence of BKV infection was high and BKV infection was associated with an increased incidence of TA-TMA/VOD and diffuse alveolar hemorrhage. Patients older than 5 years of age at the time of HSCT and treated with MMF were more likely to develop BKV infection.

The Role of Vitamin D and Vitamin D Receptor Gene Polymorphisms in the Course of Inflammatory Bowel Disease in Children

Background: The etiopathogenesis of inflammatory bowel disease (IBD) is still unclear. Prior studies suggest genetic components that may influence the incidence and severity of the disease. Additionally, it was shown that low levels of serum vitamin D may have an impact on the clinical course of the disease due to its effect on the immunological system. Methods: We aimed to investigate the correlation between the incidence of vitamin D receptor (VDR) gene polymorphisms (rs11568820, rs10735810, rs1544410, rs7975232, and rs731236, commonly described as Cdx2, FokI, Bsm, ApaI, and TaqI, respectively) and vitamin D concentration with the clinical course of IBD (disease activity, extent of the intestinal lesions). Data were obtained from 62 patients with IBD (34 with Crohn’s disease, 28 with ulcerative colitis), aged 3–18 years, and compared with controls (N = 47), aged 8–18 years. Results: Although there was no difference in the incidence of individual genotypes between the study groups (IBD, C) in all the polymorphisms examined, we described a significant increase in the chance of developing IBD for heterozygotes of Cdx2 (OR: 2.3, 95% CI 0.88–6.18, p = 0.04) and BsmI (OR: 2.07, 95% CI 0.89–4.82, p = 0.048) polymorphisms. The mean serum 25OHD level in patients with IBD was significantly higher compared with the controls (19.87 ng/mL vs. 16.07 ng/mL; p = 0.03); however, it was still below optimal (&gt;30 ng/mL). Furthermore, a significant correlation was found between vitamin D level and TaqI in patients with IBD (p = 0.025) and patients with CD (p = 0.03), as well as with the BsmI polymorphism in patients with IBD (p = 0.04) and patients with CD (p = 0.04). A significant correlation was described between the degree of disease activity and genotypes for the FokI polymorphism in patients with UC (p = 0.027) and between the category of endoscopic lesions and genotypes for the Cdx2 polymorphism also in patients with UC (p = 0.046). Conclusions: The results suggest a potential correlation of VDR gene polymorphism with the chance of developing IBD, and the clinical course of the disease requires further studies in larger group of patients. Vitamin D supplementation should be recommended in both children with inflammatory bowel disease and in healthy peers.

Long-term safety of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: post-marketing extension surveillance in Japan

Fabry disease is a rare inherited X-linked metabolic disorder in which deficient alpha-galactosidase A activity causes progressive build-up of globotriaosylceramide (Gb3) and multi-system dysfunction. Following approval of agalsidase alfa for Fabry disease in Japan in 2006, an 8-year all-case post-marketing surveillance (PMS) showed that the treatment was well tolerated and effective for managing disease progression in adult Japanese patients. The present nationwide prospective observational study extended the initial PMS by enrolling patients who continued agalsidase alfa treatment after the initial 8-year period in a 6.5-year extension survey. Patient information from the initial PMS and the extension survey was evaluated as a single data set (observation period: February 2007–September 2021). Of 493 patients in the initial PMS, 129 (45.0% male classic, 6.2% male non-classic, 48.8% female heterozygous phenotype) consented to participate in the extension survey and were included in the analysis. The mean duration of treatment was 9.6 years. A total of 145 adverse drug reactions (ADRs) occurred in 31 patients (24%), and 22 serious ADRs occurred in 12 patients (9.3%). Although serious cardiac, renal, or cerebrovascular adverse events decreased in frequency over time in male patients, serious cardiac events continued to occur in female patients, who showed higher incidence of cardiac complications at baseline. No new safety concerns were identified. Additionally, long-term agalsidase alfa treatment sustained the initial reduction in Gb3 concentrations without increasing the rate of anti-agalsidase antibody positivity. These findings suggest that agalsidase alfa treatment demonstrates continued safety and sustains patients' clinical course over the long term.