Eligible Cases Research Articles

Insulin Adjustments for Hospitalized COVID-19 Patients on a Fixed Dexamethasone Protocol

Introduction: COVID-19, in combination with steroid treatment, is known to propagate hyperglycemia in diabetic patients. The purpose of this study was to establish a new insulin protocol for diabetic patients with COVID-19 on the dexamethasone protocol for better glycemic control. Research Design and Methods: This was a retrospective cohort study conducted at NYU Langone Long Island Hospital from 1 July 2020 to 1 July 2021. Eligible cases had to meet the following inclusion criteria: age of 18 years or greater, history of or new-onset diabetes, diagnosis of COVID-19 and receiving the 10 day dexamethasone treatment, length of stay of at least 3 days with a minimum of 48 h of glucose monitoring, and requiring basal and prandial insulin with correction during hospital stay. Data were collected using the hospital’s electronic record system. The total basal, prandial, and daily doses of insulin on the day at which glycemic control was achieved, or if glycemic control was not achieved by the discharge date, then on the completion date of the dexamethasone treatment, were collected and assessed. Results: A total of 145 patient cases were analyzed. About 46% of patients achieved glycemic control. The average insulin dose required was 0.67 (0.61–0.74) unit/kg. The mean total dose of insulin was 59 units. The mean total basal dose was 21 units. The mean total prandial dose was 38 units. The average prandial doses were higher than the basal doses for all participants. Conclusions: Diabetic patients with COVID-19 on dexamethasone should be initiated on at least 0.6–0.7 u/kg of insulin to achieve glycemic control.

The association between discordant umbilical arterial resistance in growth-restricted fetuses and adverse outcomes

Assessing the umbilical artery pulsatility index via Doppler measurements plays a crucial role in evaluating fetal growth impairment. This study aimed to investigate perinatal outcomes associated with discordant pulsatility indices of umbilical arteries in fetuses with growth restriction. In this retrospective cohort study, all singleton pregnancies were included if their estimated fetal weight and/or abdominal circumference fell below the 10th percentile for gestational age (2017-2022). Eligible cases included singleton pregnancies with concurrent sampling of both umbilical arteries within 14 days of birth at the ultrasound evaluation closest to delivery. The exclusion criteria included births before 22 weeks of gestation, evidence of absent or reverse end-diastolic flow in either umbilical artery, and known fetal genetic or structural anomalies. The study compared cases with discordant umbilical artery pulsatility index values (defined as 1 umbilical artery pulsatility index at ≤95th percentile and the other umbilical artery pulsatility index at >95th percentile for gestational age) to pregnancies where both umbilical artery pulsatility indices had normal pulsatility index values and those with both umbilical arteries displaying abnormal pulsatility index values. The primary outcome assessed was the occurrence of composite adverse neonatal outcomes. Multivariable logistic regressions were performed, adjusting for relevant covariates. The study encompassed 1014 patients, including 194 patients (19.1%) with discordant umbilical artery pulsatility index values among those who had both umbilical arteries sampled close to delivery, 671 patients (66.2%) with both umbilical arteries having normal pulsatility index values, and 149 patients (14.7%) with both umbilical arteries exhibiting abnormal values. Pregnancies with discordant umbilical artery pulsatility index values displayed compromised sonographic parameters compared with those with both umbilical arteries showing normal pulsatility index values. Similarly, the number of abnormal umbilical artery pulsatility index values was associated with adverse perinatal outcomes in a dose-response manner. Cases with 1 abnormal (discordant) umbilical artery pulsatility index value showed favorable sonographic parameters and perinatal outcomes compared with cases with both abnormal umbilical artery pulsatility index values, and cases with both abnormal umbilical artery pulsatility index values showed worse sonographic parameters and perinatal outcomes compared with cases with discordant UA PI values. Multivariate analysis revealed that discordant umbilical artery pulsatility indices were significantly and independently associated with composite adverse perinatal outcomes, with an adjusted odds ratio of 1.75 (95% confidence interval, 1.24-2.47; P = .002). Evaluating the resistance indices of both umbilical arteries may provide useful data and assist in assessing adverse perinatal outcomes among fetuses with growth restriction.

Abstract 3852: Comprehensive genomic profiling of recurrent or metastatic head and neck cancer presenting with combined positive score 90 or more

Abstract Background. Biomarkers that predict response to immune checkpoint inhibitor (ICI) in recurrent metastatic squamous cell carcinoma of the head and neck (RMHNSCC) are not well known. Previously, we have found that Combined positive score (CPS) ≥90 and albumin >3.5 respond well to ICI treatment in patients with RMHNSCC treated with ICI irrespective of addition of chemotherapy. In the present study, we investigated whether RMHNSCC with CPS ≥90 has a characteristic genomic mutational profile. Methods. CPS measurements were performed on a single tumor specimen at the time of diagnosis of RMHNSCC, as approved by Japanese health insurance. Tumor specimens were obtained from the primary tumor as much as possible, and sections that best reflected anti-tumor immunity were decided by a pathologist. We retrospectively reviewed the results obtained from comprehensive genomic profiling (CGP) testing of RMHNSCC cases with CPS ≥90 who were treated by ICI experienced at our institution. Results. There were 117 eligible RMHNSCC cases. The number of primary lesions were oral cavity in 28 cases (23.9%), nasopharynx in 10 cases (8.5%), oropharynx in 21 cases (17.9%), hypopharynx in 33 cases (28.2%), and others in 18 cases (15.4%). Of 117 patients, 28 patients (23.9%) had a CPS ≥90. Of the 28 cases, the number of primary lesions were oral cavity in 12 cases (42.9%), nasopharynx in 4 cases (14.3%), oropharynx in 0 cases (0%), hypopharynx in 8 cases (28.6%), and others in 3 cases (10.7%). When ICI was administered, CPS ≥90 had a statistically significantly better prognosis than CPS <90 for OS and PFS. Of the 28 cases with CPS ≥90, CGP test was performed in 6 cases. The primary lesions in the 6 cases consisted of 3 oral cavity, 2 nasopharynx, 1 hypopharynx, and 1 maxillary sinus. All three oral primary cases had co-mutations in the TERT promoter and HRAS. Two of the nasopharyngeal primary cases had mutations in JAK3 and STAT, respectively. One of the hypopharyngeal primary cases had mutations in FGFR3. Conclusion. RMHNSCC with CPS ≥90 had unique mutations that could account the enhanced PD-L1 expression, such as TERT/HRAS co-mutation, JAK-STAT pathway mutation, and FGFR pathway mutation. The above findings may be useful for predicting the efficacy of ICI for RMHNSCC. Citation Format: Yuki Saito, Kage Hidenori, Kenya Kobayashi, Osamu Fukuoka, Koji Yamamura, Aya Shinozaki-Ushiku, Katsutoshi Oda, Kenji Kondo. Comprehensive genomic profiling of recurrent or metastatic head and neck cancer presenting with combined positive score 90 or more [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3852.

Efficacy of postmortem CT and tissue sampling in establishing the cause of death in clinical practice: a prospective observational study

AimsThe aim of this study is to evaluate whether agreement with autopsy-determined cause of death (COD) increases by use of postmortem CT (PMCT) or PMCT in combination with postmortem sampling...

Timing of readmissions for complications following emergency colectomy: follow-up beyond post-operative day 30 matters

Background and purposeEmergency colectomies are associated with a higher risk of complications compared to elective ones. A critical assessment of complications occurring beyond post-operative day 30 (POD30) is lacking. This study aimed to assess the readmission rate and factors associated with readmission 6-months following emergency colectomy.MethodsA retrospective cohort study of adult patients who underwent emergency colectomy (2010–2018) was performed using the Nationwide Readmissions Database. The cohort was divided into two groups: (i) no readmission and (ii) emergency readmission(s) for complications related to colectomy (defined using ICD-9/10 codes). Readmissions were categorized as either “early” (POD0–30) or “late” (> POD30). Differences between groups were described and multivariable regression controlling for relevant covariates defined a priori were used to identify factors associated with timing of readmission and cost.ResultsOf 141,481 eligible cases, 13.22% (n = 18,699) were readmitted within 6-months of emergency colectomy for colectomy-related complications, 61.63% of which were “late” readmissions (> POD30). The most common reasons for “late” readmission were for bleeding, gastrointestinal, and infectious complications (20.80%, 25.30%, and 32.75%, respectively). On multiple logistic regression, female gender (OR 1.12; 95%CI 1.04–1.21), open procedures (OR 1.12, 95%CI 1.011–1.24), and sigmoidectomies (OR 1.51, 95%CI 1.39–1.65, relative to right hemicolectomies) were the strongest predictors of “late” readmission. On multiple linear regression, “late” readmissions were associated with a $1717.09 USD (95%CI $1717.05–$1717.12) increased cost compared to “early” readmissions.DiscussionThe majority of colectomy-related readmissions following emergency colectomy occur beyond POD30 and are associated with cases that are of overall higher morbidity, as well as open sigmoidectomies. Given the associated increased cost of care, mitigation of such readmissions by close follow-up prior to and beyond POD30 is advisable.

MRI 3D SPACE T2WI for Pituitary Adenoma Cavernous Sinus Invasion Diagnosis

ObjectiveThis study aims to assess the utility of MRI 3D SPACE T2WI sequences in evaluating cavernous sinus invasion by pituitary adenomas. Materials and methodsData were collected from patients who underwent continuous pituitary MRI examinations at the Medical Imaging Center of our hospital from October 2019 to February 2021. Eligible cases were evaluated for sagittal and axial T1WI sequences, coronal 3D SPACE T2WI sequences, and sagittal and coronal enhanced T1WI sequences using the INFINITT PACS workstation. The Wilcoxon signed-rank test for paired samples and the Mann–Whitney U test for two independent samples were used to statistically analyze differences in image quality scores among various groups. In addition, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each observation index were compared with intraoperative results. Results3D SPACE T2WI showed superior cavernous sinus imaging quality compared with CE T1WI and T2WI plain scans (P<0.05). The sensitivity, specificity, PPV, and NPV were 100%, 90.0%, 55.60%, and 100.0%, respectively. The accuracy for pituitary adenoma invasiveness diagnosis based on cavernous sinus medial wall integrity was 94.40%. ConclusionThe imaging quality of the medial wall of the cavernous sinus on the 3D SPACE T2WI plain scan sequence surpassed that of CE T1WI TSE-enhanced scans and T2WI TSE plain scans. The continuous observation of the medial wall of the cavernous sinus using this sequence holds great diagnostic value for assessing cavernous sinus invasion by pituitary adenomas. This strategy is more reliable than traditional MRI observation indicators.

Prognostic and Predictive Value of Immunoscore in Stage III Colorectal Cancer: Pooled Analysis of Cases From the SCOT and IDEA-HORG Studies.

Immunoscore (IS) is prognostic in stage III colorectal cancer (CRC) and may predict benefit of duration (6 v 3 months) of adjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. We sought to determine IS prognostic and predictive value in stage-III CRC treated with adjuvant FOLFOX or oral capecitabine and infusional oxaliplatin (CAPOX) in the SCOT and IDEA-HORG trials. Three thousand sixty-one cases had tumor samples, of which 2,643 (1,792 CAPOX) were eligible for IS testing. Predefined cutoffs (IS-Low and IS-High) were used to classify cases into two groups for analysis of disease-free survival (3-year DFS) and multivariable-adjusted hazard ratios (mvHRs) by Cox regression. IS was determined in 2,608 (99.5%) eligible cases, with 877 (33.7%) samples classified as IS-Low. IS-Low tumors were more commonly high-risk (T4 and/or N2; 52.9% IS-Low v 42.2% IS-High; P < .001) and in younger patients (P = .024). Patients with IS-Low tumors had significantly shorter DFS in the CAPOX, FOLFOX, and combined cohorts (mvHR, 1.52 [95% CI, 1.28 to 1.82]; mvHR, 1.58 [95% CI, 1.22 to 2.04]; and mvHR, 1.55 [95% CI, 1.34 to 1.79], respectively; P < .001 all comparisons), regardless of sex, BMI, clinical risk group, tumor location, treatment duration, or chemotherapy regimen. IS prognostic value was greater in younger (≤65 years) than older (>65 years) patients in the CAPOX cohort (mvHR, 1.92 [95% CI, 1.50 to 2.46] v 1.28 [95% CI, 1.01 to 1.63], PINTERACTION = .026), and in DNA mismatch repair proficient than deficient mismatch repair disease (mvHR, 1.68 [95% CI, 1.41 to 2.00] v 0.67 [95% CI, 0.30 to 1.49], PINTERACTION = .03), although these exploratory analyses were uncorrected for multiple testing. Adding IS to a model containing all clinical variables significantly improved prediction of DFS (likelihood ratio test, P < .001) regardless of MMR status. IS is prognostic in stage III CRC treated with FOLFOX or CAPOX, including within clinically relevant tumor subgroups. Possible variation in IS prognostic value by age and MMR status, and prediction of benefit from extended adjuvant therapy merit validation.

Current trends and barriers to video management and analytics as a tool for surgeon skilling.

The benefits of intraoperative recording are well published in the literature; however, few studies have identified current practices, barriers, and subsequent solutions. The objective of this study was to better understand surgeon's current practices and perceptions of video management and gather blinded feedback on a new surgical video recording product with the potential to address these barriers effectively. A structured questionnaire was used to survey 230 surgeons (general, gynecologic, and urologic) and hospital administrators across the US and Europe regarding their current video recording practices. The same questionnaire was used to evaluate a blinded concept describing a new intraoperative recording solution. 54% of respondents reported recording eligible cases, with the majority recording less than 35% of their total eligible caseload. Reasons for not recording included finding no value in recording simple procedures, forgetting to record, lack of access to equipment, legal concerns, labor intensity, and difficulty accessing videos. Among non-recording surgeons, 65% reported considering recording cases to assess surgical techniques, document practice, submit to conferences, share with colleagues, and aid in training. 35% of surgeons rejected recording due to medico-legal concerns, lack of perceived benefit, concerns about secure storage, and price. Regarding the concept of a recording solution, 74% of all respondents were very likely or quite likely to recommend the product for adoption at their facility. Appealing features to current recorders included the product's ease of use, use of AI to maintain patient and staff privacy, lack of manual downloads, availability of full-length procedural videos, and ease of access and storage. Non-recorders found the immediate access to videos and maintenance of patient/staff privacy appealing. Tools that address barriers to recording, accessing, and managing surgical case videos are critical for improving surgical skills. Touch Surgery Enterprise is a valuable tool that can help overcome these barriers.

Plasma Soluble Angiotensin-Converting Enzyme 2 and Risk of Recurrent Stroke: A Nested Case-Control Analysis

Introduction: The angiotensin-converting enzyme 2 (ACE-2) and its shedding product (soluble ACE-2 [sACE-2]) are implicated in adverse cardiovascular outcomes. However, the relationship between sACE-2 and stroke recurrence is unknown. Herein, we examined the relationship of sACE-2 with stroke recurrence in patients with ischemic stroke or transient ischemic attack. Methods: Data were obtained from the Third China National Stroke Registry (CNSR-III). Eligible cases consisted of 494 patients who developed recurrent stroke within 1-year follow-up, and 494 controls were selected using age- and sex-matched with a 1:1 case-control ratio. Conditional logistic regressions were used to evaluate the association between sACE-2 and recurrent stroke. The main outcomes were recurrent stroke within 1 year. Results: Among 988 patients included in this study, the median (interquartile range) of sACE-2 was 25.17 (12.29–45.56) ng/mL. After adjustment for conventional confounding factors, the odds ratio (OR) with 95% confidence interval (CI) in the highest quartile versus the lowest quartile was 1.68 (1.12–2.53) for recurrent stroke within 1-year follow-up. Subgroup analysis showed that the association between elevated plasma level of sACE-2 and stroke recurrence was significant in patients with higher systemic inflammation, as indicated by high-sensitivity C-reactive protein ≥ 2 mg/L (adjusted OR: 2.33 [95% CI, 1.15–4.72]) and neutrophil counts ≥ median (adjusted OR: 2.66 [95% CI, 1.35–5.23]) but not significant in patients with lower systemic inflammation. Discussion/Conclusion: Elevated plasma sACE-2 concentration was associated with increased risk of recurrent stroke.

Prodromal symptoms of rheumatoid arthritis in a primary care database: variation by ethnicity and socioeconomic status.

To assess whether prodromal symptoms of rheumatoid arthritis (RA), as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between January 1st 2004 to May 1st 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI, and smoking status. White ethnicity and the highest socioeconomic quintile were comparators. In total, 70115 cases were eligible for inclusion, of which 66.4% female. Twenty-one symptoms were coded in > 0.1% of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (OR 1.71, 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82). There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data.

Natural history and clinical features of hepatitisC virus infection during childhood: A nationwide, observational survey in Japan.

Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitisC viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan. We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases. Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1years (range 0.9-7.2years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0months; p=0.0031). Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.

Impact and utility of follicular lymphoma GELF criteria in routine care: an Australasian Lymphoma Alliance study.

Follicular lymphoma (FL) treatment initiation is largely determined by tumor burden and symptoms. In the pre-rituximab era, the Group d'Etude des Lymphomes Folliculaires (GELF) developed widely adopted criteria to identify high tumor burden FL patients to harmonize clinical trial populations. The utilization of GELF criteria (GELFc) in routine therapeutic decision- making is poorly described. This multicenter retrospective study evaluated patterns of GELFc at presentation and GELFc utilization in therapeutic decision-making in newly diagnosed, advanced-stage rituximab-era FL. Associations between GELFc, treatment given, and patient survival were analyzed in 300 eligible cases identified between 2002-2019. One hundred and sixty-three (54%) had ≥1 GELFc at diagnosis. The presence or cumulative number of GELFc did not predict progression-free survival in patients undergoing watch-and-wait (W&W) or those receiving systemic treatment. Of interest, in patients with ≥1 GELFc, 16 of 163 (10%) underwent initial W&W (comprising 22% of the W&W cohort). In those receiving systemic therapy +/- radiotherapy, 74 of 215 (34%) met no GELFc. Our data suggest clinicians are using adjunctive measures to make decisions regarding treatment initiation in a significant proportion of patients. By restricting FL clinical trial eligibility only to those meeting GELFc, reported outcomes may not be applicable to a significant proportion of patients treated in routine care settings.

A preliminary study on the spasticity reduction of quadriceps after selective dorsal rhizotomy in pediatric cases of spastic cerebral palsy.

This study aimed to evaluate the potential alleviation of quadriceps spasticity in children diagnosed with spastic cerebral palsy (CP) following selective dorsal rhizotomy (SDR). A retrospective study was conducted on children suffering from spastic CP who underwent SDR at the Department of Neurosurgery, Shanghai Children's Hospital, from July 2018 to September 2020. Inclusion criteria comprised children exhibiting quadriceps spasticity exceeding modified Ashworth Scale grade 2. Muscle tone and motor function were assessed before the operation, at short-term follow-up and at the last follow-up after SDR. Additionally, intraoperative neurophysiological monitoring data were reviewed. The study comprised 20 eligible cases, where, prior to surgery, 35 quadriceps muscles exhibited spasticity exceeding modified Ashworth Scale grade 2. Following short-term and mid-term follow-up, specifically an average duration of 11 ± 2 days and 1511 ± 210 days after SDR, it was observed that muscle tension in adductors, hamstrings, gastrocnemius, and soleus decreased significantly. This reduction was accompanied by a decrease in quadriceps muscle tone in 24 out of 35 muscles (68.6%). Furthermore, the study found that intraoperative electrophysiological parameters can predict postoperative spasticity relief in the quadriceps. The triggered electromyographic (EMG) output of the transected sensory root/rootlets after single-pulse stimulation revealed that the higher the EMG amplitudes in quadriceps, the greater the likelihood of postoperative decrease in quadriceps muscle tension. SDR demonstrates the potential to reduce muscle spasticity in lower extremities in children diagnosed with CP, including a notable impact on quadriceps spasticity even they are not targeted in SDR. The utilization of intraoperative neurophysiological monitoring data enhances the predictability of quadriceps spasticity reduction following SDR.

Use of artificial hydration in patients diagnosed with senility as the cause of death by home care physicians: A cross₋sectional study.

The aim of this study was to investigate the frequency, effectiveness, and reasons for the use of artificial hydration (AH) in senile patients in the last week, and patient-related factors associated with its usage. Between April and May 2023, I conducted a cross₋sectional study among medical institutions affiliated with the Japan Network of Home Care Supporting Clinics. Eligible cases included those in which senility was listed as the cause of death on the death certificate from January 1, 2022, to December 31, 2022. The questions asked use of AH, reasons for AH, and symptoms that improved or worsened with AH. Patient characteristics, including age, gender, place of death, length of treatment, and complication of dementia, were also asked. Descriptive statistics were performed. Univariate and multivariate analyses were conducted to examine the association between patient characteristics and the use of AH. Eighty-three medical institutions (12.5%) provided responses, contributing a total of 714 cases. AH was administered in 236 cases (33.1%). The most common reason was "due to family preference" in 110 cases (46.6%). One hundred thirty-five cases (57.2%) reported "no improved symptoms," while symptom worsening was reported as "no worsened symptoms" in 176 cases (74.6%). Multivariate analysis on 699 cases using complete-case analysis identified age (risk ratio [RR]:0.98, 95% confidence interval [CI]: 0.96-0.99) and female (RR:0.73, 95% CI:0.58-0.92) as factors associated with the use of AH. This study revealed that AH was commonly used based on family preferences and to alleviate psychological burdens on the family.

Identifying in-market application of Pelargonium root extract EPs 7630 for the treatment of COVID-19: analysis of pharmacovigilance data.

Introduction: Phytopharmaceutical products are successfully used for acute respiratory infections and may therefore be promising candidates for adjuvant symptomatic treatment of COVID-19. In vitro and clinical studies suggest that the proprietary Pelargonium sidoides DC. root extract EPs 7630 has antiviral and immunomodulatory properties, and effects on SARS-CoV-2 propagation have been shown in vitro. Medicinal products containing the extract have been approved for the symptomatic treatment of acute viral respiratory tract infections. Methods: We present a retrospective review of case reports submitted spontaneously to the pharmacovigilance database of the manufacturer of EPs 7630 and containing information on the off-label use of the extract for the treatment and prophylaxis of COVID-19 and of post-COVID-19 syndrome. Eligible case reports were identified by automated database searches. Results: Forty-four case reports filed between December 2019 and February 2023 were eligible for analysis. More than ¾ described the use of EPs 7630 for treatment of COVID-19 while the remaining reports referred to the treatment of post-COVID-19 syndrome or to COVID-19 prophylaxis. 15/22 cases which reported on treatment duration indicated an intake of EPs 7630 for up to 7days. Five case reports indicated the use of EPs 7630 as COVID-19 monotherapy while 14 indicated a combination treatment with other drugs. All 28 cases that reported on treatment outcome characterized the patients as improved. Thirty case reports (68%) did not indicate any complications. The most frequent suspected adverse reactions were gastrointestinal complaints and hypersensitivity reactions, both of which may occur as known adverse effects of EPs 7630. No unexpected adverse reactions were observed. Conclusion: Reported cases confirm that there was a certain off-label use of EPs 7630 for COVID-19 in the market. Even though no formal conclusions about the efficacy of EPs 7630 in COVID-19 can be drawn, a beneficial effect would be explainable by the pharmacological profile of the extract. Further assessment of the effects of EPs 7630 in COVID-19-related indications therefore appears to be both justified and promising, particularly as the available case reports did not give rise to any safety concerns also in this patient group.

Cytomegalovirus Diseases of the Gastrointestinal Tract in Immunocompetent Patients: A Narrative Review.

Cytomegalovirus (CMV) is a potential pathogen that causes gastrointestinal (GI) tract diseases regardless of host immunity. In contrast to immunocompromised individuals, immunocompetent patients lack a comprehensive overview of the gastrointestinal manifestations. This study aims to provide a comprehensive summary of the current evidence regarding presentations, diagnostics, management, risk assessment, and outcomes in immunocompetent patients with CMV GI disease. A thorough literature search of English publications up to April 2022 was conducted across electronic databases to identify relevant articles, with eligible case series selected for detailed analysis. The majority of immunocompetent patients affected by CMV GI disease are typically elderly, critically ill, or burdened with comorbidities that compromise immunity. Clinical presentations range from subtle symptoms to severe surgical conditions, including instances of mortality. Specific clinical presentations, blood test results, or endoscopic features are lacking, necessitating reliance on histopathological tests such as immunohistochemistry staining for diagnosis. While antiviral therapy may offer benefits in improving outcomes, careful individual assessment is warranted due to diverse comorbidities and potential side effects. Mortality rates vary considerably based on underlying medical conditions and therapeutic approaches. It is imperative for clinicians to maintain vigilance for CMV GI disease among high-risk groups, despite their baseline immunocompetence, in order to enhance clinical outcomes.

Real-word application of the AT(N) classification and disease-modifying treatment eligibility in a hospital-based cohort.

The AT(N) classification system stratifies patients based on biomarker profiles, including amyloid-beta deposition (A), tau pathology (T), and neurodegeneration (N). This study aims to apply the AT(N) classification to a hospital-based cohort of patients with cognitive decline and/or dementia, within and outside the Alzheimer's disease (AD) continuum, to enhance our understanding of the multidimensional aspects of AD and related disorders. Furthermore, we wish to investigate how many cases from our cohort would be eligible for the available disease modifying treatments, such as aducanemab and lecanemab. We conducted a retrospective evaluation of 429 patients referred to the Memory Center of IRCCS San Raffaele Hospital in Milan. Patients underwent clinical/neuropsychological assessments, lumbar puncture, structural brain imaging, and positron emission tomography (FDG-PET). Patients were stratified according to AT(N) classification, group comparisons were performed and the number of eligible cases for anti-β amyloid monoclonal antibodies was calculated. Sociodemographic and clinical features were similar across groups. The most represented group was A + T + N + accounting for 38% of cases, followed by A + T - N + (21%) and A - T - N + (20%). Although the clinical presentation was similar, the A + T + N + group showed more severe cognitive impairment in memory, language, attention, executive, and visuospatial functions compared to other AT(N) groups. Notably, T + patients demonstrated greater memory complaints compared to T - cases. FDG-PET outperformed MRI and CT in distinguishing A + from A - patients. Although 61% of the observed cases were A + , only 17% of themwere eligible for amyloid-targeting treatments. The AT(N) classification is applicable in a real-world clinical setting. The classification system provided insights into clinical management and treatment strategies. Low cognitive performance and specific regional FDG-PET hypometabolism at diagnosis are highly suggestive for A + T + or A - T + profiles. This work provides also a realistic picture of the proportion of AD patients eligible for disease modifying treatments emphasizing the need for early detection.

The importance of considering competing risks in recurrence analysis of intracranial meningioma

BackgroundThe risk of recurrence is overestimated by the Kaplan–Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan–Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated.MethodsWe surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan–Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions.ResultsOf 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan–Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions).ConclusionThe importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

A Novel Method of Calculating the Drained Liver Volume Using a 3D Volume Analyzer for Biliary Drainage of Unresectable Malignant Hilar Biliary Obstruction

ObjectivesIn patients with unresectable malignant hilar biliary obstruction (UMHBO), drainage of ≥ 50% liver volume correlates with better clinical outcomes. Accurately measuring the liver volume to be drained by biliary stents is required. We aimed to develop a novel method for calculating the drained liver volume (DLV) using a 3D volume analyzer (3D volumetry), and assess the usefulness for drainage in patients with UMHBO.MethodsThree-dimensional volumetry comprises the following steps: (1) manual tracing of bile duct using 3D imaging system; (2) 3D reconstruction of bile duct and liver parenchyma; and (3) calculating DLV according to the 3D distribution of bile ducts. Using 3D volumetry, we reviewed data of patients who underwent biliary drainage for UMHBO, calculated the DLV, and determined the association between DLV and biliary drainage outcome.ResultsThere were 104 eligible cases. The mean DLV was 708 ± 393 ml (53% ± 21%). and 65 patients (63%) underwent drainage of ≥50% liver volume. The clinical success rate was significantly higher in patients with DLV ≥ 50% than in patients with DLV < 50% (89% vs. 28%, P < 0.001). The median time to recurrence of biliary obstruction (TRBO) and survival time were significantly longer in patients with DLV ≥ 50% than in patients with DLV < 50% (TRBO, 292 vs. 119 days, P = 0.03; survival, 285 vs. 65days, P = 0.004, log-rank test, respectively).ConclusionsThree-dimensional volumetry, a novel method to calculate DLV accurately according to bile duct distribution was useful for drainage in UMHBO patients.

Epidemiology, Characteristics, and Prognostic Factors of Primary Atypical Teratoid/Rhabdoid Tumors in the Spinal Canal: A Systematic Review.

Primary atypical teratoid/rhabdoid tumors (AT/RTs) in the spinal canal are rare central nervous system (CNS) neoplasms that are challenging to diagnose and treat. To date, there has been no standard treatment regimen for these challenging malignant tumors. Thus, we conducted this research to explore potential prognostic factors and feasible treatment modalities for improving the prognosis of these tumors. Articles were retrieved from the PubMed, MEDLINE, and Embase databases, using the keywords "atypical teratoid/rhabdoid tumor," "rhabdoid tumor," "spine," "spinal," "spinal neoplasm", and "spinal cord neoplasm." All eligible cases demonstrated SMARCB1-deficient expression validated by pathological examination. We collected and analyzed data related to clinical presentation, radiological features, pathological characteristics, treatment modalities and prognosis via Kaplan-Meier and Cox regression analyses. Thirty-six articles comprising 58 spinal AT/RT patients were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 18 and 22 months, respectively. Kaplan-Meier analysis demonstrated significant survival improvements for OS in the nonmetastasis, male, radiotherapy and intrathecal chemotherapy groups as well as for PFS in the chemotherapy and radiotherapy groups. Multivariate analysis revealed that chemotherapy and radiotherapy were prognostic factors for improved PFS, and that intrathecal chemotherapy reduced the risk of mortality. Spinal AT/RTs are uncommon malignant entities with a dismal survival rate. Although our review is limited by variability between cases, there is some evidence revealing potential risk factors and the importance of systematic chemotherapy, intrathecal chemotherapy and radiotherapy in spinal AT/RT treatment modalities.