Similar Clinical Profiles Research Articles

Bladder Cancer in Young Patients: Management and Outcomes

Background and Objective: Bladder cancer frequently occurs between the ages of 50 years and 70 years and rarely occurs before the age of 40 years. It accounts for 1% - 4% of all cases of cancer. This study focuses on the clinical, etiological, histological, therapeutic, and evolutive profiles of patients with bladder cancer aged less than 45 years. Materials and Methods: This retrospective study was carried out over seven years (from January 2014 to December 2020) on 15 patients below 45 years of age who were being treated for bladder cancer. The diagnosis was made in all patients via cystoscopy and abdominal computerized tomography, while the nature, grade, and degree of infiltration were determined via endoscopic resection and pathology. Results: The mean age of the 15 patients in this study was 34.4 ± 5.19 years. In 86.6% of cases, the patients had macroscopic hematuria as the main presenting complaint. Twelve patients (80%) had bladder tumors that did not infiltrate the muscle. These patients were followed up clinically. In 86.6% of cases, there was a single tumor with a mean diameter of 2.53 cm. In four patients (26.6%), mitomycin was started early. The overall rates of tumor recurrence and progression were 26.6% and 20%, respectively. Conclusion: Bladder cancer also occurs in young people, with similar clinical and epidemiological profiles as exists in elderly patients. The prognosis of bladder cancer in young people depends on the treatment method chosen by the physician.

Epidemiology and Characteristics of Chronic Pancreatitis-Do the East and West Meet?

Previous large studies on the epidemiology and clinical profile of chronic pancreatitis have suggested significant differences in presentation and management in the eastern and western hemispheres. The aim of this systematic review was to compare large multicenter studies across different geographic regions of the world to detect meaningful differences in the presentation and management of this poorly understood disease. We identified 237 manuscripts through a comprehensive literature review aiming to identify multicenter studies enrolling more than 200 patients to limit reporting biases. After rigorous screening, 12 studies were included for the final analysis. The Asian studies were included in the eastern cohort, and the European and American studies were included in the western cohort. Reported demographics, risk factors, etiologies, clinical presentation, complications, and management strategies were then compared. We found similar demographics across both cohorts including age, prevalence among gender, and predominant etiology. Clinical manifestations including pain, pancreatic calcifications, and diabetes were similar between both cohorts although pseudocysts, pancreatic cancer, and strictures were more common in the west. Notably opioids and surgical/endotherapy management were more common in the west as well. Chronic pancreatitis is a protracted disease affecting predominantly middle-aged people, leading to a decreased quality of life. Chronic pancreatitis now appears to have a fairly similar clinical profile and natural history in the east and west. There is notable variability in management. We hope that international collaboration may identify common targets for research which could lead to significant advances in the understanding and management of chronic pancreatitis.

The efficacy of cystoperitoneal shunting for the surgical management of intracranial arachnoid cysts in the elderly: A systematic review of the literature.

Background: Intracranial arachnoid cysts (AC) are benign, cerebrospinal fluid filled spaces within the arachnoid layer of the meninges. Neurosurgical intervention in children and young adults has been extensively studied, but the optimal strategy in the elderly remains unclear. Therefore, we performed a single center retrospective study combined with a systematic review of the literature to compare cystoperitoneal (CP) shunting with other surgical approaches in the elderly cohort.Methods: Retrospective neurosurgical database search between January 2005 and December 2018, and systematic review of the literature using PRISMA guidelines were performed. Inclusion criteria: Age 60 years or older, radiological diagnosis of intracranial AC, neurosurgical intervention, and neuroradiological (NOG score)/clinical outcome (COG score). Data from both sources were pooled and statistically analyzed.Results: Our literature search yielded 12 studies (34 patients), which were pooled with our institutional data (13 patients). CP shunts (7 patients; 15%), cyst fenestration (28 patients; 60%) and cyst marsupialisation/resection (10 patients; 21%) were the commonest approaches. Average duration of follow-up was 23.6, 26.9, and 9.5 months for each approach, respectively. There was no statistically significant association between choice of surgical intervention and NOG score (P = 0.417), COG score (P = 0.601), or complication rate (P = 0.955). However, CP shunting had the lowest complication rate, with only one patient developing chronic subdural haematoma.Conclusion: CP shunting is a safe and effective surgical treatment strategy for ACs in the elderly. It has similar clinical and radiological outcomes but superior risk profile when compared with other approaches. We advocate CP shunting as first line neurosurgical intervention for the management of intracranial ACs in the elderly.

125 Sex differences in myocarditis natural history

Abstract Aims The role of sex in determining the profile and the outcomes of patients with myocarditis is widely unexplored. Our study seeks to evaluate the impact of sex as a modifier factor in the clinical characterization and natural history of patients with definite diagnosis of myocarditis. Methods and results We retrospectively analysed a single-centre cohort of consecutive patients with definite diagnosis (i.e., endomyocardial biopsy or cardiac magnetic resonance proven) of myocarditis. A sub-analysis was performed after division of population according to the main symptom of presentation (i.e., chest pain, ventricular arrhythmias, and heart failure). Clinical and echocardiographic data were evaluated at diagnosis and at last available evaluation (i.e., median of 30 months). The study outcome measure was a composite of all-cause mortality or heart transplantation. We enrolled 312 patients (187; 60% presenting with chest pain; 19; 6% with ventricular arrhythmias; 106; 34% with heart failure). Most of patients (211, 68% of the whole population) were males, consistently in the three modes of presentation. Despite no clinically relevant differences were found at baseline presentation, males presented a larger indexed left ventricular end-diastolic volume (LVEDVi) (62 ± 23 vs. 52 ± 20, P = 0.011 in males vs. females respectively) at follow-up evaluation. At a median follow-up of 62 months, 36 (17%) males vs. females experienced death or heart transplantation (Log-rank P = 0.037). At multivariable Cox analysis, male sex emerged as a predictor of mortality (HR: 2.358; 1.044–5.322; P = 0.039 and left ventricular ejection fraction (LVEF) < 50% (HR: 8.169; 1.226–54.425; P = 0.030)]. Results were consistent in patients presenting with heart failure and chest pain, while arrhythmic group was too small to be reliably interpreted. Conclusions In a large cohort of patients with definite diagnosis of myocarditis, females experienced a more favorable long-term prognosis than male, despite a similar clinical profile at baseline.

Longitudinal clinical, cognitive and neuroanatomical changes over five years in GBA‐positive Parkinson’s disease patients

AbstractBackgroundGlucocerebrosidase gene (GBA) mutations are the greatest genetic cause of Parkinson’s disease (PD). The aim of this study was to monitor the longitudinal disease course of PD patients with GBA mutation (GBA‐positive) at diagnosis compared to PD noncarriers (GBA‐negative) along a 5‐year follow‐up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and subcortical volumes.Method10 GBA‐positive and 20 GBA‐negative PD at diagnosis underwent clinical, neuropsychological and brain MRI assessments at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared in terms of cortical thickness and subcortical volumes to a group of 22 age‐matched healthy controls (HC). Clinical, cognitive and cortical/subcortical MRI features were compared between groups at baseline and over time.ResultAt baseline, GBA‐positive and GBA‐negative patients had similar clinical and cognitive profiles. Compared to GBA‐negative and HC, GBA‐positive patients showed cortical thinning of left temporal, parietal and occipital gyri. Over time, compared to GBA‐negative, GBA‐positive worsened significantly in motor and cognitive symptoms, and showed a greater pattern of bilateral cortical thinning involving also frontal cortices. After 60 months, compared to HC, GBA‐negative PD patients showed a pattern of cortical thinning similar to that shown by GBA‐positive at baseline. The two groups of patients showed similar patterns of subcortical volume loss over time.ConclusionCompared to GBA‐negative patients, GBA‐positive PD showed a greater and earlier cortical thinning which worsened over time. GBA‐negative PD patients reached the pattern of cortical thinning of GBA‐positive at the baseline only after 5 years, reflecting a slower disease progression. This study highlights the importance of the early detection of GBA mutation in PD patients. Funding: This study was supported by the Ministry of Education and Science of the Republic of Serbia (Grant #175090).

The role of thyroid hormones in the differential diagnosis of tuberculous and parapneumonic pleural effusions

BackgroundThe differential diagnosis of tuberculous pleural effusion (TPE) and parapneumonic pleural effusion (PPE) is challenging due to similar clinical manifestations and body fluid biochemical profiles. Thyroid hormone levels change in response to lymphocyte proliferation in the peripheral blood of patients with mycobacterial infections such as tuberculosis; therefore, this study aimed to investigate the utility of assessing thyroid hormone levels to aid in the differential diagnosis of TPE and PPE. MethodsWe measured free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels in the pleural effusions of 59 newly admitted patients (32 and 27 with TPE and PPE, respectively). Hormone levels were assessed using an electrochemiluminescence technique, and the diagnostic parameters for tuberculosis were evaluated. Differences in hormone levels between patients with TPE and PPE were assessed by t-tests, and their diagnostic value for a differential diagnosis was evaluated by receiver operating characteristic curve analyses. ResultsFT3 and FT4 levels in patients with TPE were significantly higher than those in patients with PPE (p < 0.01 and p < 0.05, respectively), whereas TSH expression did not significantly differ between the two groups (p > 0.05). FT3 and FT4 levels showed no correlation with sex or history of smoking, although FT3 levels decreased with age. The highest sensitivity was observed for the quantification of FT3 levels (84.38%). ConclusionsIncreased FT3 and FT4 levels could potentially be used for the differential diagnosis of TPE and PPE.

Expanded Use of the One-Step Technique for Simultaneous Landing Zone Stenting and Placement of the Melody Transcatheter Pulmonary Valve.

We report a multicenter experience with simultaneous right ventricular outflow tract (RVOT) stenting and transcatheter pulmonary valve implantation using the Melody valve (Medtronic). Prestenting the RVOT before Melody valve implantation is now the standard of care. Prestenting is usually performed as a separate step. The "one-step" technique for simultaneous landing zone stenting and Melody delivery was previously reported using only Max LD stents (Medtronic). We report a multicenter experience of simultaneous stenting and Melody implantation using multiple stent types in combination. This retrospective cohort study includes 33 patients from 3 centers who underwent simultaneous stenting and Melody valve implantation between 2017 and 2020. Key variables were compared with 31 patients from the same centers who underwent standard (non-simultaneous) prestenting followed by Melody implantation during the same time frame. The 2 groups were similar in terms of age, weight, sex, and total procedure time. The 2 groups had similar clinical results and safety profiles, with no difference between the postimplantation right ventricle (RV) to pulmonary artery systolic pressure gradient, RV to aortic pressure ratio, and complication rate. The simultaneous group had lower radiation exposure as measured by dose area product. Up to 3 stents were safely placed simultaneously with a Melody valve. Simultaneous RVOT stenting and Melody valve implantation can safely be used to place up to 3 stents outside a Melody valve. This approach can simplify the catheterization procedure and potentially reduce radiation dose.

Clinical Outcomes of Oligomonocytic Chronic Myelomonocytic Leukemia (OM-CMML) and Predictive Factors of Evolution of OM-CMML into Overt Chronic Myelomonocytic Leukemia (CMML)

INTRODUCTIONRecent studies have shown that OM-CMML and CMML have a similar clinical and biological profile. Since the proliferative-CMML (P-CMML) is the last-stage of CMML proliferative continuum and shows poor outcomes, it is expected that OM-CMML presents the best outcomes of these entities, as it represents an early-stage of dysplastic-CMML (D-CMML). In this sense, although a high percentage of OM-CMML evolve to CMML, some of them die before evolving. Therefore, identifying predictive factors of evolution into CMML may be valuable since, OM-CMML that evolves to CMML show shorter overall survival (OS) (Calvo X et al. Blood Adv 2020).AIMTo analyze clinical outcomes of 41 OM-CMML patients and to compare them to that of 182 overt CMML (141 D-CMML and 41 P-CMML), and to assess predictive factors of evolution of OM-CMML into overt CMML.RESULTSOM-CMML showed longer OS than D-CMML and P-CMML (Figure 1). OM-CMML also showed longer AML-free survival than D-CMML (median OS: 131.8m vs. 43.47m; P=0.001) and P-CMML (median OS: 23m; P<0.01). These outcomes were retained after multivariate adjustment by CPSS (HR:0.38, 95%CI 0.21-0.70, P=0.002; HR:2.53, 95%CI 1.64-3.91, P=<0.001), CPSS-P (HR:0.42, 95%CI 0.23-0.78, P=0.005; HR:2.82, 95%CI 1.92-4.14, P=<0.001), and Mayo-prognostic-model (HR:0.41, 95CI 0.23-0.75, P=0.04; HR:3.45, 95%CI 2.29-5.20, P=<0.001). At a median follow-up of 45 months, 29% of D-CMML evolved to P-CMML. There was no difference in OS between D-CMML patients that evolved to P-CMML than those who did not. Nevertheless, from the moment of evolution, they had a very short survival (median OS: 10.2 months). This suggests that P-CMML evolution is the latest stage of a biological continuum that initiates in OM-CMML. Reinforcing this idea, mutations associated with proliferation (i.e: ASXL1 and RAS-pathway) were identified as independent prognostic factors for OS in our series (HR ASXL1:2.47, 95%CI 1.13-5.37, P=0.023; HR RAS-pathway:3.91, 95%CI 1.74-8.77, P=0.001).As previously commented, OM-CMML patients who evolved to overt CMML showed an inferior OS than did those who did not. At a median follow-up of 42 months, 30% OM-CMML evolved to CMML. Patients with more than 3 mutated genes (HR: 4.24, 95%CI 1.08-16.71, P=0.039) and a proportion of monocytes above 20% in peripheral blood (HR: 3.48, 95%CI 1.05-11.47, P=0.041) showed a significant shorter time to CMML. These two variables were faced in a multivariate analysis and maintained their significance for predicting time to CMML (HR: 4.33, 95%CI 1.23-15.20, P=0.022; and HR:5.82, 95%CI 1.32-25.7 , P=0.02). Moreover, these variables were also independent adverse prognostic factors for OS in our series of 94 patients with available molecular data (41 OM-CMML and 53 CMML) (HR:4.39, 95%CI 1.99-9.68 , P<0.001; HR:3.05 , 95%CI 1.27-7.34 , P=0.013). Figure 2 depicts univariate survival analysis. Given the similar HR for predicting time to CMML of both variables, we implemented a model for predicting time to CMML: 0 points (none of them), 1 (one of them) or 2 points (both). This model offered an excellent predictive power (C-index: 0.82).CONCLUSIONS1. The clinical outcomes of OM-CMML support its consideration as the first step in the proliferative continuum of CMML.2. OM-CMML with higher molecular complexity and higher relative monocytosis are at greater risk of CMML evolution. [Display omitted] DisclosuresBellosillo: Thermofisher Scientific: Consultancy, Speakers Bureau; Roche: Research Funding, Speakers Bureau; Qiagen: Consultancy, Speakers Bureau.

Clinical features and outcome of COVID-19 among PLHIV in Gujarat, India: A case series.

Information on people living with HIV (PLHIV) and current COVID-19 pandemic is still scarce in Indian setting. This case series of PLHIV with COVID-19 describes clinical characteristics and outcome in this special group of patients. This case series included 11 confirmed cases of COVID-19 among PLHIV admitted at a tertiary care hospital in Gujarat, India during April–December 2020. This retrospective study was conducted by doing secondary data analysis from case records of patients for various variables including demographic, clinical characteristics, HIV-related parameters, and outcome (discharged/death). The mean age of patients was 39.2 years ranging from 20 to 55 years. Nearly, 18% (2/11) of patients had major comorbidities like diabetes and hypertension. All were taking antiretroviral therapy drugs with >95% drug adherence and had CD4 count ranging from 79/cu.mm. to 1189/cu.mm. Majority (91%) of patients recovered and were discharged while only one patient (9%) died during course of COVID-19 treatment. COVID-19 showed a similar clinical and epidemiological profile among PLHIV like other group of people. Further studies with large-sample size are recommended to find risks of COVID-19 among PLHIV and its impact on treatment outcomes.

Deep significance clustering: a novel approach for identifying risk-stratified and predictive patient subgroups.

ObjectiveDeep significance clustering (DICE) is a self-supervised learning framework. DICE identifies clinically similar and risk-stratified subgroups that neither unsupervised clustering algorithms nor supervised risk prediction algorithms alone are guaranteed to generate.Materials and MethodsEnabled by an optimization process that enforces statistical significance between the outcome and subgroup membership, DICE jointly trains 3 components, representation learning, clustering, and outcome prediction while providing interpretability to the deep representations. DICE also allows unseen patients to be predicted into trained subgroups for population-level risk stratification. We evaluated DICE using electronic health record datasets derived from 2 urban hospitals. Outcomes and patient cohorts used include discharge disposition to home among heart failure (HF) patients and acute kidney injury among COVID-19 (Cov-AKI) patients, respectively.ResultsCompared to baseline approaches including principal component analysis, DICE demonstrated superior performance in the cluster purity metrics: Silhouette score (0.48 for HF, 0.51 for Cov-AKI), Calinski-Harabasz index (212 for HF, 254 for Cov-AKI), and Davies-Bouldin index (0.86 for HF, 0.66 for Cov-AKI), and prediction metric: area under the Receiver operating characteristic (ROC) curve (0.83 for HF, 0.78 for Cov-AKI). Clinical evaluation of DICE-generated subgroups revealed more meaningful distributions of member characteristics across subgroups, and higher risk ratios between subgroups. Furthermore, DICE-generated subgroup membership alone was moderately predictive of outcomes.DiscussionDICE addresses a gap in current machine learning approaches where predicted risk may not lead directly to actionable clinical steps.ConclusionDICE demonstrated the potential to apply in heterogeneous populations, where having the same quantitative risk does not equate with having a similar clinical profile.

A case of severe multi-system disease in a sickle cell SC patient caused by parvovirus B19 infection

Sickle Cell Disease (SCD) is an inherited hemoglobinopathy, which results in production of abnormal hemoglobin S. HbSC disease is a variant of SCD, which shares a similar clinical complication profile to HbSS disease, but often thought to be a milder condition. In patients with SCD, Hb S in deoxygenated state undergoes polymerization, leading to hemolysis, vaso-occlusive events, and eventually end-organ damage. Among other complications in patients with SCD is increased risk of complications caused by parvovirus B19. We present a case of a 14-year-old female with HbSC disease who presented to the emergency room with complaint of abdominal pain and found to have splenic sequestration. Splenic sequestration progressed rapidly, Hemoglobin (hb) dropped to 4.6 g/dl and acute chest syndrome (ACS) developed. She was treated following the ACS protocol, received 4 units of Packed Red Blood Cells (PRBC) and subsequently underwent a single volume PRBC exchange transfusion. Considering her unusual presentation, with severe ARDS from alveolar hemorrhage requiring mechanical ventilation and multi-organ injury, several autoimmune and infectious conditions with a cytokine storm component including COVID-19 disease, were considered. Results of viral testing revealed parvovirus B19 IgM antibodies signifying an acute infection. She fully recovered with supportive care and was discharged home. Multisystem involvement simulating connective tissue disorders or malignancies with acute parvovirus B19 infection has been reported and is considered extremely rare. To our knowledge, there were no reports of pediatric patients with SC disease presenting with splenic sequestration and ACS in the setting of parvovirus B19 multisystem disease. Keywords: sickle cell disease; acute respiratory distress syndrome; acute chest syndrome; parvovirus B19.

Gender differences in characteristics and outcomes in heart failure patients referred for end-stage treatment.

AimsDespite signals from clinical trials and mechanistic studies implying different resilience to heart failure (HF) depending on gender, the impact of gender on presentation and outcomes in patients with HF remains unclear. This study assessed the impact of gender on clinical presentation and outcomes in patients with HF referred to a specialised tertiary HF service.Methods and resultsConsecutive patients with HF referred to a specialised tertiary HF service offering advanced therapy options including left ventricular assist devices (LVAD) and heart transplantation were prospectively enrolled from August 2015 until March 2018. We assessed clinical characteristics at baseline and performed survival analyses and age‐adjusted Cox regression analyses in men vs. women for all‐cause death and a combined disease‐related endpoint comprising death, heart transplantation, and LVAD implantation. Analyses were performed for the overall study population and for patients with HF with reduced ejection fraction (HFrEF). Of 356 patients included, 283 (79.5%) were male. The median age was 58 years (interquartile range 50–67). Two hundred and fifty‐one (74.5%) patients had HFrEF. HF aetiology, ejection fraction, functional status measures, and most of the cardiac and non‐cardiac comorbidities did not differ between men and women. In a median follow‐up of 3.2 years, 50 patients died (45 men, 5 women), 15 patients underwent LVAD implantation, and 8 patients heart transplantation. While all‐cause death was not significantly different between both genders in the overall population [16.9 vs. 6.0%, P = 0.065, hazard ratio (HR) 2.29 (95% confidence interval 0.91–5.78), P = 0.078], in the HFrEF subgroup, a significant difference between men and women was observed [20.7% vs. 3.9%, P = 0.017, HR 3.67 (95% confidence interval 1.13–11.91), P = 0.031]. The combined endpoint was more often reached in men than in women in both the overall population [21.6% vs. 9.0%, P = 0.053, HR 2.51 (1.08–5.82), P = 0.032] and the HFrEF subgroup [27.1% vs. 7.7%, P = 0.015, HR 3.58 (1.29–9.94), P = 0.014].ConclusionsPatients referred to a specialised tertiary HF service showed a similar clinical profile without relevant gender differences. In the mid‐term follow‐up, more male than female patients died or underwent heart transplantation and LVAD implantation. These findings call for independent validation and for further research into gender‐specific drivers of HF progression.

Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive Parkinson's disease patients.

To study the longitudinal disease course of Parkinson's disease (PD) patients with glucocerebrosidase (GBA) mutation (GBA-positive) compared to PD non-carriers (GBA-negative) along a 5-year follow-up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and gray-matter (GM) volumes. Ten GBA-positive and 20 GBA-negative PD patients underwent clinical, neuropsychological, and MRI assessments (cortical thickness and subcortical, hippocampal, and amygdala volumes) at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared with 22 age-matched healthy controls. Clinical, cognitive, and MRI features were compared between groups at baseline and over time. At baseline, GBA-positive and GBA-negative PD patients had similar clinical and cognitive profiles. Compared to GBA-negative and controls, GBA-positive patients showed cortical thinning of left temporal, parietal, and occipital gyri. Over time, compared to GBA-negative, GBA-positive PD patients progressed significantly in motor and cognitive symptoms, and showed a greater pattern of cortical thinning of posterior regions, and frontal and orbito-frontal cortices. After 5 years, compared to controls, GBA-negative PD patients showed a pattern of cortical thinning similar to that showed by GBA-positive cases at baseline. The two groups of patients showed similar patterns of subcortical, hippocampal, and amygdala volume loss over time. Compared to GBA-negative PD, GBA-positive patients experienced a more rapid motor and cognitive decline together with a greater, earlier and faster cortical thinning. Cortical thickness measures may be a useful tool for monitoring and predicting PD progression in accordance with the genetic background.

Diagnosis and classification of headache associated with sexual activity using a composite algorithm: A cohort study.

To differentiate primary headache associated with sexual activity from other devastating secondary causes. In this prospective cohort, we recruited consecutive patients with at least 2 attacks of headache associated with sexual activity from the headache clinics or emergency department of a national medical center from 2005 to 2020. Detailed interview, neurological examination, and serial thorough neuroimaging including brain magnetic resonance imaging and magnetic resonance angiography scans were performed on registration and during follow-ups. Patients were categorized into four groups, i.e. primary headache associated with sexual activity, reversible cerebral vasoconstriction syndrome, probable reversible cerebral vasoconstriction syndrome, and other secondary headache associated with sexual activity through a composite clinic-radiological diagnostic algorithm. We compared the clinical profiles among these groups, including sex, age of onset, duration, quality, and clinical course ("chronic" indicates disease course ≥ 1 year). In addition, we also calculated the score of the reversible cerebral vasoconstriction syndrome2, a scale developed to differentiate reversible cerebral vasoconstriction syndrome from other intracranial vascular disorders. Overall, 245 patients with headache associated with sexual activity were enrolled. Our clinic-radiologic composite algorithm diagnosed and classified all patients into four groups, including 38 (15.5%) with primary headache associated with sexual activity, 174 (71.0%) with reversible cerebral vasoconstriction syndrome, 26 (10.6%) with probable reversible cerebral vasoconstriction syndrome, and 7 (2.9%) with other secondary causes (aneurysmal subarachnoid hemorrhage (n = 4), right internal carotid artery dissection (n = 1), Moyamoya disease (n = 1), and meningioma with hemorrhage (n = 1)). These four groups shared similar clinical profiles, except 26% of the patients with primary headache associated with sexual activity had a 3 times greater chance of running a chronic course (≥ 1 year) than patients with reversible cerebral vasoconstriction syndrome. Of note, the reversible cerebral vasoconstriction syndrome2 score could not differentiate reversible cerebral vasoconstriction syndrome from other groups. Our composite clinic-radiological diagnostic algorithm successfully classified repeated headaches associated with sexual activity, which were predominantly secondary and related to vascular disorders, and predicted the prognosis. Primary headache associated with sexual activity and reversible cerebral vasoconstriction syndrome presented with repeated attacks of headache associated with sexual activity may be of the same disease spectrum.

Chronic Prurigo: Similar Clinical Profile and Burden Across Clinical Phenotypes.

Chronic prurigo is a debilitating skin disease characterized by the presence of chronic pruritus and scratching-related pruriginous lesions. The pruriginous lesions can differ in their clinics what has recently been categorized into different clinical phenotypes. The most common one is chronic nodular prurigo (syn. prurigo nodularis); other phenotypes are papular, plaque, umbilicated, and linear prurigo. A comparison between these phenotypes regarding similarities and differences has not yet been performed. In this explorative analysis, itch characteristics, scratching behavior, and disease burden of the nodular, papular, plaque, and umbilicated prurigo were investigated in 1,128 patients. Patients with nodular and plaque prurigo were younger than patients with papular and umbilicated prurigo. The shortest duration of the underlying pruritus was found in papular and umbilicated prurigo, the longest in plaque prurigo. Itch intensity, impairment of sleep, mood and the quality of life did not differ. These findings confirm that the clinical phenotypes of chronic prurigo belong to a spectrum of one disease with similar disease characteristics and can be categorized under the umbrella term of chronic prurigo. Future clinical trials should include all phenotypes of chronic prurigo.

Women Have Lower Mortality Than Men After Attending a Long-Term Medically Supervised Exercise Program.

Medically supervised exercise programs (MSEPs) are equally recommended for men and women with cardiovascular disease (CVD). Aware of the lower CVD mortality in women, we hypothesized that among patients attending a MSEP, women would also have better survival. Data from men and women, who were enrolled in a MSEP between 1994 and 2018, were retrospectively analyzed. Sessions included aerobic, resistance, flexibility and balance exercises, and cardiopulmonary exercise test was performed. Date and underlying cause of death were obtained. Kaplan-Meier methods and Cox proportional hazards regression were used for survival analysis. A total of 2236 participants (66% men, age range 33-85 yr) attended a median of 52 (18, 172) exercise sessions, and 23% died during 11 (6, 16) yr of follow-up. In both sexes, CVD was the leading cause of death (39%). Overall, women had a more favorable clinical profile and a longer survival compared to men (HR = 0.71: 95% CI, 0.58-0.85; P < .01). When considering those with coronary artery disease and similar clinical profile, although women had a lower percentage of sex- and age-predicted maximal oxygen uptake at baseline than men (58 vs 78%; P < .01), after adjusting for age, women still had a better long-term survival (HR = 0.68: 95% CI, 0.49-0.93; P = .02). Survival after attendance to a long-term MSEP was better among women, despite lower baseline cardiorespiratory fitness. Future studies should address whether men and women would similarly benefit when participating in an MSEP.

Identification of Similar Patients Through Medical Concept Embedding from Electronic Health Records: A Feasibility Study for Rare Disease Diagnosis.

To identify patients with similar clinical profiles and derive insights from the records and outcomes of similar patients can help fast and precise diagnosis and other clinical decisions for rare diseases. Similarity methods are required to take into account the semantic relations between medical concepts and also the different relevance of all medical concepts presented in patients' medical records. In this paper, we introduce the methods developed in the context of rare disease screening/diagnosis from clinical data warehouse using medical concept embedding and adjusted aggregations. Our methods provided better preliminary results than baseline methods, with a significant improvement of precision among the top ranked similar patients, which is encouraging for further fine-tuning and application on a large-scale dataset for new/candidate patient identification.

A multi-centre phase 3 study comparing efficacy and safety of Bemfola® versus Gonal-f® in women undergoing ovarian stimulation for IVF

Bemfola (follitropin alfa) (Finox AG, Switzerland), a new recombinant FSH, has a comparable pharmacological profile to that of Gonal-f (Merck Serono, Germany), the current standard for ovarian stimulation. A randomized, multi-centre, Phase 3 study in women undergoing IVF or intracytoplasmic sperm injection (n = 372) showed Bemfola yielding similar efficacy and safety profiles to Gonal-f. Women aged 20–38 years of age were randomized 2:1 to receive a single, daily, subcutaneous 150 IU dose of either Bemfola or Gonal-f. This study tested equivalence in the number of retrieved oocytes using a pre-determined clinical equivalence margin of ±2.9 oocytes. Compared with Gonal-f, Bemfola treatment resulted in a statistically equivalent number of retrieved oocytes (Bemfola 10.8 ± 5.11 versus Gonal-f 10.6 ± 6.06, mean difference: 0.27 oocytes, 95% confidence interval: -1.34–1.32) as well as a similar clinical pregnancy rate per embryo transfer in first and second cycles (Bemfola: 40.2% and 38.5%, respectively; Gonal-f: 48.2% and 27.8%, respectively). No difference in severe ovarian hyperstimulation syndrome was observed between treatment groups (Bemfola: 0.8%; Gonal-f: 0.8%). This study demonstrates similar clinical efficacy and safety profiles between Bemfola and Gonal-f, and suggests that Bemfola can be an appropriate alternative in ovarian stimulation protocols.

Patient with Lobular Carcinoma of the Breast and Activating AKT1 E17K Variant

To present the characteristics of the AKT1E117K gene variant and a description of the clinical application in a patient with metastatic breast cancer. 63 y/o woman with Stage IV Invasive lobular carcinoma at diagnosis was treated with Palbociclib and aromatase inhibitors (AI). At progression, tissue was sent for comprehensive genomic profiling to Foundation Medicine (FM) which revealed AKT1E17K mutation. In lieu of available clinical data within the patient's tumor type (HR+ HER2- breast cancer), extrapolated data from the Flatiron Health-FM (FH-FMI) Clinico-genomic Database (CGDB) was discussed at our Molecular Tumor Board (MTB). After multidisciplinary discussion, the consensus recommendation was to start treatment with the combination of mTOR inhibitor everolimus, and AI, exemestane. Patient tolerated treatment without major side effects. By the second clinical visit the patient's breast showed signs of improvement. PET/CT showed diminished left axillary uptake, decreased right paratracheal lymph node PET avidity, and stable bone disease consistent with a partial response. The most recent office visit in January 2021, breast exam revealed a normal-appearing skin with only faint erythema. All other skin lesions have resolved. Although, the role of AKT1 variant described here is not well defined and therapeutic significance of M-Tor inhibitors not established in metastatic breast cancers, comprehensive approach to this case unraveled new and successful therapeutic option in this patient. This demonstrates that applying available Precision Medicine tools like MTB and real world data sets from patient populations with similar clinical and genomic profiles may provide more options for treatment.

Comparison of urinary protein-to-creatinine ration, serum albumin, serum creatinine and systolic arterial blood pressure of glomerular injury cases in dogs with chronic kidney disease

This study aims at assessing the prevalence of glomerular alterations in dogs with chronic kidney disease (CKD) and comparing the clinical and laboratory parameters. The tests conducted include a double-blind histopathological assay conducted by two pathologists, urine tests including inactive sediment, urinary protein-to-creatinine (UPC), serum albumin and serum creatinine, as well as measurement of the systolic arterial blood pressure. The prevalence of glomerular injuries was determined and the predominant injury was compared with a group comprised of the remaining injuries. The study included 24 dogs with CKD. The results revealed a predominance of membranous glomerular alterations 17/24 (70,83%), followed by glomerulosclerosis 3/24 (12,50%), membranoproliferative injuries 2/24, glomerulocystic atrophy 1/24 and glomerular amyloidosis 1/24. Amyloidosis presented the highest UPC while the membranoproliferative injury presented the lowest mean concentration of serum albumin. Higher values in the UPC did not correspond with lower mean serum albumin values. Glomerulosclerosis presented the highest mean systolic blood pressure and glomerular atrophy presented the highest creatinine values. When comparing membranous injuries with a group comprised of the remaining injuries, the UPC did not present significant differences between the groups. Renal amyloidosis was included in the group with the lowest systolic arterial blood pressure values while membranoproliferative injury was included in the group with highest UPC. The group called “others” presented the highest creatinine value. Dogs with CKD may present several types of glomerular injuries with similar clinical and laboratory profiles. This study observed a predominance of membranous glomerular injuries, followed by membranoproliferative injuries, glomerulocystic atrophy and amyloidosis.