Specific Features Of Patients Research Articles

Computational Simulation of Virtual Patients Reduces Dataset Bias and Improves Machine Learning-Based Detection of ARDS from Noisy Heterogeneous ICU Datasets.

Goal: Machine learning (ML) technologies that leverage large-scale patient data are promising tools predicting disease evolution in individual patients. However, the limited generalizability of ML models developed on single-center datasets, and their unproven performance in real-world settings, remain significant constraints to their widespread adoption in clinical practice. One approach to tackle this issue is to base learning on large multi-center datasets. However, such heterogeneous datasets can introduce further biases driven by data origin, as data structures and patient cohorts may differ between hospitals. Methods: In this paper, we demonstrate how mechanistic virtual patient (VP) modeling can be used to capture specific features of patients' states and dynamics, while reducing biases introduced by heterogeneous datasets. We show how VP modeling can be used for data augmentation through identification of individualized model parameters approximating disease states of patients with suspected acute respiratory distress syndrome (ARDS) from observational data of mixed origin. We compare the results of an unsupervised learning method (clustering) in two cases: where the learning is based on original patient data and on data derived in the matching procedure of the VP model to real patient data. Results: More robust cluster configurations were observed in clustering using the model-derived data. VP model-based clustering also reduced biases introduced by the inclusion of data from different hospitals and was able to discover an additional cluster with significant ARDS enrichment. Conclusions: Our results indicate that mechanistic VP modeling can be used to significantly reduce biases introduced by learning from heterogeneous datasets and to allow improved discovery of patient cohorts driven exclusively by medical conditions.

Enhancing pre-trained contextual embeddings with triplet loss as an effective fine-tuning method for extracting clinical features from electronic health record derived mental health clinical notes

The development and application of real-world evidence in the field of mental health trails other therapeutic areas like oncology and cardiovascular diseases, largely because of the lack of frequent, structured outcomes measures in routine clinical care. A wealth of valuable patient-level clinical data resides in an unstructured format in clinical notes documented at each clinical encounter. Manual extraction of this information is not scalable, and heterogeneity in recording patterns and the heavily context-dependent nature of the content renders keyword-based automated searches of little practical value. While state-of-the-art natural language processing (NLP) models based on the transformer architecture have been developed for information extraction tasks in the mental health space, they are not trained on unstructured clinical data that capture the nuances of different dimensions of mental health (e.g., symptomology, social history, etc.). We have developed a novel transformer architecture-based NLP model to capture core clinical features of patients with major depressive disorder (MDD). Initialized on MentalBERT model weights, we pre-trained our model further on clinical notes from routine mental health care and fine-tuned using triplet loss, an effective feature embedding regularizer which boosts classification and extraction of 3 specific features in patients with MDD: anhedonia, suicidal ideation with plan or intent (SP), and suicidal ideation without plan or intent (SI) or where plan or intent are unknown. Training and testing data were annotated by mental health clinicians. Using triplet loss for fine tuning led to improvement in model performance benchmarked against other standard models (MentalBERT and BioClinicalBERT) on the same tasks, achieving F1 scores of 0.99 for anhedonia, 0.94 for SP, and 0.88 for SI. Model robustness was tested by testing sensitivity of model predictions on modifications to test sentences. The application of such an NLP model can be further scaled to capture clinical features of other disorders as well as other domains like social history or history of illness.

Expanded carrier screening for reproductive risk assessment: An evidence-based practice guideline from the National Society of Genetic Counselors.

Expanded carrier screening (ECS) intends to broadly screen healthy individuals to determine their reproductive chance for autosomal recessive (AR) and X-linked (XL) conditions with infantile or early-childhood onset, which may impact reproductive management (Committee Opinion 690, Obstetrics and Gynecology, 2017, 129, e35). Compared to ethnicity-based screening, which requires accurate knowledge of ancestry for optimal test selection and appropriate risk assessment, ECS panels consist of tens to hundreds of AR and XL conditions that may be individually rare in various ancestries but offer a comprehensive approach to inherited disease screening. As such, the term "equitable carrier screening" may be preferable. This practice guideline provides evidence-based recommendations for ECS using the GRADE Evidence to Decision framework (Guyatt et al., BMJ, 2008, 336, 995; Guyatt et al., BMJ, 2008, 336, 924). We used evidence from a recent systematic evidence review (Ramdaney et al., Genetics in Medicine, 2022, 20, 374) and compiled data from peer-reviewed literature, scientific meetings, and clinical experience. We defined and prioritized the outcomes of informed consent, change in reproductive plans, yield in identification of at-risk carrier pairs/pregnancies, perceived barriers to ECS, amount of provider time spent, healthcare costs, frequency of severely/profoundly affected offspring, incidental findings, uncertain findings, patient satisfaction, and provider attitudes. Despite the recognized barriers to implementation and change in management strategies, this analysis supported implementation of ECS for these outcomes. Based upon the current level of evidence, we recommend ECS be made available for all individuals considering reproduction and all pregnant reproductive pairs, as ECS presents an ethnicity-based carrier screening alternative which does not rely on race-based medicine. The final decision to pursue carrier screening should be directed by shared decision-making, which takes into account specific features of patients as well as their preferences and values. As a periconceptional reproductive risk assessment tool, ECS is superior compared to ethnicity-based carrier screening in that it both identifies more carriers of AR and XL conditions as well as eliminates a single race-based medical practice. ECS should be offered to all who are currently pregnant, considering pregnancy, or might otherwise biologically contribute to pregnancy. Barriers to the broad implementation of and access to ECS should be identified and addressed so that test performance for carrier screening will not depend on social constructs such as race.

Online group psychodynamic psychotherapy-The effectiveness and role of attachment-The results of a short study.

The role of remote treatment, including psychotherapy, has increased during the COVID-19 pandemic. The results of research in this area are promising, initially pointing to similar effectiveness for online psychotherapy as that of face-to-face psychotherapy. A significantly smaller amount of research has been conducted on online group psychotherapy, in particular, in the psychodynamic paradigm. Many authors have drawn attention to the need to conduct further research, considering specific patient features, for example, personality traits, attachment style, age, and other demographic variables. This study conducted pre- and post-treatment (10 weeks) and a 6-week follow-up, on the effectiveness of online synchronous group psychodynamic psychotherapy (via Zoom) taking into account patients’ attachment styles. Four main hypotheses were tested: H1: Patients will obtain a lower score in the attachment’s dimensions of anxiety and avoidance; H2: Patients will get a lower level of symptoms and sense of loneliness; H3: Patients will have increased self-esteem; and H4: The anxiety and avoidance dimensions of the attachment will be predictors for the effectiveness of online psychodynamic group psychotherapy. Twenty-two outpatients participated in the study, out of which 18 suffered from neurotic, stress-related, and somatoform disorders (F40-F48), and four suffered from a depressive episode (F32.0, F32.1) according to ICD-10. The results of the pre-treatment test showed a reduction in the global severity of psychiatric symptoms (d = −0.526) and depressive symptoms (d = −0.5), as well as an increase in self-esteem (d = 0.444) and feelings of loneliness (d = 0.46). A change in the attachment dimension, anxiety (d = −0.557) and avoidance (d = −0.526), was also observed. The above results were maintained in the follow-up test conducted after 6 weeks. Additionally, a reduction in the symptoms of social phobia was observed. Attachment dimensions were not a predictor of the effectiveness of psychotherapy, but a decrease in avoidance during therapy was a predictor of increased symptoms of pain. The results of the research are promising in terms of psychiatric symptoms and increased self-esteem. During therapy, there may be a favorable change in attachment dimensions, but this variable was not shown to be a predictor of results. These results suggest that more controlled research is required.

Using large databases to study cancer genomics in an undergraduate classroom

Cancer databases collect original cancer studies and patient clinical information into one site that allows for global analysis. While many courses focus on cancer, few utilize these powerful cancer databases. Our goal was to create a lab experience in which students could explore original cancer study databases, looking at the expression and incidence of driver mutations of cancer. First, the students focus on a specific patient including demographic data and type of cancer. Then the students analyze mRNA expression levels associated with mutations of the gene, determining if it is a tumor suppressor or oncogene. Students also learn which mutations are actionable and how they affect survival. In summary, this module allows students to analyze global trends in driver mutations in cancers and dive into specific patient features.

Plasticity of natural killer cells in pregnant patients infected with SARS-CoV-2 and their neonates during childbirth.

The COVID-19 pandemic has occurred due to infection caused by the SARS-CoV-2 coronavirus, which impacts gestation and pregnancy. In SARS-CoV-2 infection, only very rare cases of vertical transmission have been reported, suggesting that fetal immune imprinting due to a maternal infection is probably a result of changes in maternal immunity. Natural killer (NK) cells are the leading maternal immune cells that act as a natural defense system to fight infections. They also play a pivotal role in the establishment and maintenance of pregnancy. While peripheral NK cells display specific features in patients infected with SARS-CoV-2 in the general population, information remains elusive in pregnant mothers and neonates. In the present study, we analyzed the characteristics of NK cells isolated from both neonatal umbilical cord blood and maternal peripheral blood close to the time of delivery. Phenotype and functions were compared in 18 healthy pregnant women and 34 COVID-19 patients during pregnancy within an ongoing infection (PCR+; N = 15) or after recovery (IgG+PCR−; N = 19). The frequency of NK cells from infected women and their neonates was correlated with the production of inflammatory cytokines in the serum. The expression of NKG2A and NKp30, as well as degranulation of NK cells in pregnant women with ongoing infection, were both negatively correlated to estradiol level. Furthermore, NK cells from the neonates born to infected women were significantly decreased and also correlated to estradiol level. This study highlights the relationship between NK cells, inflammation, and estradiol in patients with ongoing infection, providing new insights into the impact of maternal SARS-CoV-2 infection on the neonate.

Different Phenotypes Represent Advancing Stages of ABCA4-Associated Retinopathy: A Longitudinal Study of 212 Chinese Families From a Tertiary Center.

PurposeTo evaluate the nature and association of different phenotypes associated with ABCA4 mutations in Chinese.MethodsAll patients were recruited from our pediatric and genetic eye clinic. Detailed ocular phenotypes were characterized. The disease course was evaluated by long-term follow-up observation, with a focus on fundus changes. Cox regression was used to identify the factors associated with disease progression.ResultsA systematic review of genetic and clinical data for 228 patients and follow-up data for 42 patients indicated specific features in patients with two ABCA4 variants. Of 185 patients with available fundus images, 107 (57.8%) showed focal lesions restricted to the central macula without flecks. Among these 107 patients, 30 patients (28.0%) initially presented with relatively preserved visual acuity and inconspicuous performance on routine fundus screening. A pigmentary change in the posterior pole was observed in 22 of 185 patients (11.9%), and this change mimicked retinitis pigmentosa in 10 cases (45.5%). Follow-up visits and sibling comparisons demonstrated disease progression from cone-rod dystrophy, Stargardt disease, to retinitis pigmentosa. An earlier age of onset was associated with a more rapid decrease in visual acuity (P = 0.03). Patients with two truncation variants had an earlier age of onset.ConclusionPhenotypic variation in ABCA4-associated retinopathy may represent sequential changes in a single disease: early-stage Stargardt disease may resemble cone-rod dystrophy, whereas the presence of diffuse pigmentation in the late stage may mimic retinitis pigmentosa. Recognizing the natural progression of fundus changes, especially those visualized by wide-field fundus autofluorescence, is valuable for diagnostics and therapeutic decision-making.

Clinical and Genetic Predictors of Glycemic Control and Weight Loss Response to Liraglutide in Patients with Type 2 Diabetes.

Background: Evidence suggests a heterogeneous response to therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to identify the genetic and clinical factors that relate to glycemic control and weight loss response to liraglutide among patients with T2DM. Methods: The medical records of 116 adults with T2DM (51% female, mean body mass index 35.4 ± 6.4 kg/m2), who had been on treatment with liraglutide for at least 6 months and were genotyped for CTRB1/2 rs7202877 (T > G) polymorphism, were evaluated. Clinical and laboratory parameters were measured at baseline, 3, and 6 months after initiating liraglutide treatment. The good glycemic response was defined as one of the following: (i) achievement of glycated hemoglobin (HbA1c) < 7% (ii) reduction of the baseline HbA1c by ≥1%, and (iii) maintenance of HbA1c < 7% that a patient already had before switching to liraglutide. Weight loss responders were defined as subjects who lost ≥3% of their baseline weight. Results: Minor allele frequency was 16%. Individuals were classified as glycemic control and weight loss responders (81 (70%) and 77 (66%), respectively). Carriers of the rs7202877 polymorphic allele had similar responses to liraglutide treatment in terms of glycemic control (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.4, 3.8, p = 0.69) and weight loss (OR: 1.12, 95% CI: 0.4, 3.2, p = 0.84). In the multivariable analysis, higher baseline HbA1c (adjusted OR: 1.45, 95% CI: 1.05, 2.1, p = 0.04) and lower baseline weight (adjusted OR: 0.97, 95% CI: 0.94, 0.99, p = 0.01) were associated with better glycemic response to liraglutide, while higher baseline weight was associated with worse weight response (adjusted OR: 0.97, 95% CI: 0.95, 0.99, p = 0.02). Conclusions: Specific patient features can predict glycemic and weight loss response to liraglutide in individuals with T2DM.

Specific Features of Patients Under 40 Years Old With Small-to-Medium-Sized Arterial Deterioration.

BackgroundArterial deterioration is mostly caused by atherosclerosis, which progresses with age. However, we have observed serious backgrounds or etiologies in younger patients with non-atherosclerotic diseases and deterioration of small-to-medium-sized arterial lesions. Therefore, we aimed to identify the specific features of patients aged <40 years with deterioration of small-to-medium-sized arteries.MethodsWe selected patients who were admitted to our department from 1995 to 2019 with deterioration of small-to-medium-sized arteries (aneurysms, dissection, rupture, or arterial injury/damage) and focused on the cohort aged <40 years. We examined the backgrounds or etiologies of the patients including genetic and inflammatory diseases, which might have caused the arterial deterioration.ResultsConsequently, more than half (54.1%) of the patients aged <40 years had non-atherosclerotic comorbid diseases. However, the number of deteriorated arterial lesions was higher in patients aged <40 years than in patients aged ≥40 years (3.13 vs. 1.33 lesion/patient; P = 0.011). Furthermore, the data analysis of patients with multiple arterial lesions (≥3) revealed that the younger population tended to have more specific backgrounds or etiologies, notably Ehlers-Danlos syndrome and Behçet's disease. There were no differences in the all-cause mortality and cardiovascular disease-related mortality between patients aged <40 and ≥40 years (P = 0.89 and 0.29, respectively).ConclusionsOver 50% of patients aged <40 years with deterioration of small-to-medium-sized arteries had non-atherosclerotic, specific clinical backgrounds or etiologies, including genetic and inflammatory diseases. In addition, they exhibited more arterial lesions than older patients.

Machine Learning Reimagined: The Promise of Interpretability to Combat Bias.

Machine Learning Reimagined: The Promise of Interpretability to Combat Bias.

The Role of Uric Acid in Acute and Chronic Coronary Syndromes.

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA’s relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events.

Specific Features of Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic and progressive disease of the biliary tract. PSC is strongly associated with inflammatory bowel disease (IBD), mainly with ulcerative colitis, and most PSC patients have underlying IBD. The pathophysiological interactions between IBD and PSC are unclear, although it seems that the patients with IBD and PSC have a distinct phenotype. IBD with coexisting PSC is more extensive and is characterized by milder activity compared to IBD alone. The coexistence of PSC increases the risk for colorectal cancer in IBD patients and lifelong annual surveillance colonoscopy is recommended. Also, liver transplantation (LT) for PSC may affect the course of IBD. In addition, the management of IBD after LT includes many specific problems. On the other hand, the effect of IBD on the natural history of PSC appears to be milder. However, IBD may increase the risk of postsurgical complications after LT and is a risk factor for recurrent PSC after LT. Overall, the coexistence of IBD with PSC changes the management, natural history and prognosis of both diseases.

Factors Associated With Cardiorespiratory Fitness at Completion of Cardiac Rehabilitation: Identification of Specific Patient Features Requiring Attention

BackgroundWe aimed to determine and compare predictors of postcardiac rehabilitation (CR) cardiorespiratory fitness (CRF), improvements in a large cohort of subjects with varying baseline CRF levels completing CR for ischemic heart disease and to refine prediction models further by baseline CRF. MethodsThe Alberta Provincial Project for Outcomes Assessment in Coronary Heart disease (APPROACH) and TotalCardiology (TotalCardiology, Inc, Calgary, Alberta, Canada) databases were used retrospectively to obtain information on 10,732 (1955 [18.2%] female; mean age 60.4, standard deviation [SD] 10.5 years) subjects who completed the 12-week comprehensive CR program between 1996 and 2016. Peak metabolic equivalents (METs) were determined at program start and completion and identified patients at baseline with low fitness (L-Fit) (< 5 METs), moderate fitness (M-Fit, 5-8 METs), or high fitness (H-Fit, > 8 METs). Multivariable linear regression models were developed to predict METs at completion of the program. ResultsAcross all fitness groups, mean baseline METs was the strongest predictor of CRF at completion of CR. Other factors—including sex, age, current smoking status, obesity, and diabetes—were highly predictive of post-CR CRF (all P < 0.05). Compared with H-fit patients, coronary artery bypass graft and chronic obstructive pulmonary disease in L-Fit patients, and cerebrovascular disease in M-Fit patients had an additional negative effect on the overall model variance in post-CR CRF. ConclusionExpected CRF at the end of CR is highly predictable, with several key patient factors being clear determinants of CRF. Although most identified patient factors are not modifiable, our analysis highlights populations that may require extra attention over the course of CR to attain maximal benefit.

Specific Patient Features Affect Antiepileptic Drug Therapy Decisions: Focus on Gender, Age, and Psychiatric Comorbidities.

Patient features, apart from the type of seizures/epilepsy, affect markedly antiepileptic drug (AED) choice and dosage. The present review focuses on gender, age and psychiatric comorbidities which play a leading role in influencing antiepileptic treatment. Reviews with large population of patients, controlled clinical trials, observational investigations, experimental studies and experimental reviews of experimental data, where appropriated, were analysed and illustrated to produce the most homogeneous indications possible. Different and also contradictory observations have been highlighted to stimulate a critical approach to specific aspects. Women of childbearing age should avoid valproic (VPA), acid, since this drug doubles the risk of major malformations and causes in the exposed offspring reduced intellectual development and disorders of autistic spectrum. The drug is also associated with hormonal disorders, polycystic ovary and reduced fertility. Children treated with valproic acid or phenobarbital can exhibit hyperactivity, nervousness and attention disorders. As a consequence of increased drug elimination, younger children require higher doses as compared to adults and older patients. Elderly patients treated with phenobarbital may face the risk of cognitive disorders and/or falls resulting in bone fractures. Fractures are also facilitated by carbamazepine-induced osteoporosis. Psychiatric disorders are frequently associated with epilepsy and evidence has been gained that common pathological steps underlie these conditions. Depressed patients should avoid drugs like phenobarbital, topiramate, levetiracetam, zonisamide and perampanel since these drugs can induce mood disorders. Although not conclusive, literature data indicate that topiramate and levetiracetam and also tiagabine and vigabatrin, are associated with suicidal thought/behaviour. Conversely, lamotrigine, carbamazepine, VPA and oxcarbazepine exert beneficial effects on mood. Bupropion, clomipramine, amoxapine and maprotyline among antidepressants, and clozapine, olanzapine and quietapine among antipsychotics have been observed to lower seizure threshold. Serum AED concentration monitoring is of help in dosage adjustments, especially in very young children, in patients with cognitive decline and in patients with psychiatric comorbidities. A careful evaluation of the patient variables analysed in the present review is useful to personalize and optimize AED therapy.

Use of the McGRATH™ MAC: To view or not to view?

BackgroundDue to the life-threatening consequences that a failed tracheal intubation entails, many efforts have been made to identify specific patient features, which may predict difficulty during tracheal intubation. In addition, debate exists as to whether or not video-assisted laryngoscopy (VAL) should replace direct laryngoscopy and if airway practitioners will lose their skills associated with direct laryngoscopy, now that VAL use has increased in clinical practice. AimThis study was designed to determine the first attempt success rate of tracheal intubation with the McGRATH™ MAC laryngoscope using direct visualization in patients with known difficult airways, as well as exploring the possibility of identifying a particular direct Cormack-Lehane (C-L) grade view where indirect (video) visualization can be most beneficial during laryngoscopy and intubation. MethodsFollowing IRB/ethical board approval and written informed consent, 100 adult patients (age > 18 years) with an ASA status I-III and a BMI < 50 kg/m2 who met ≥ 2 of the following inclusion criteria: Mallampatti class: III-IV, reduced mouth opening < 4 cm, neck circumference (>40 cm for females, > 43 cm for males), thyromental distance < 6 cm, ratio of the patient's height to thyromental distance ≥ 23.5 cm, sternomental distance < 12 cm, requiring general anesthesia for an elective surgery, were enrolled into this study. Patient demographic characteristics and intervening outcomes, such as initial modified C-L grade view for both direct and indirect laryngoscopy, first-attempt success rate, and the time required for a successful intubation with the McGRATH™ MAC, were recorded. ResultsOut of the 94 patients that were included in the data analysis, 72 (76.6%) were successfully intubated via direct laryngoscopy and 16 (17%) were successfully intubated via indirect (video) laryngoscopy on the first attempt with the McGRATH™ MAC (P = 0.59). This translates to an overall first-attempt success rate of 96.15% (n = 88). Six patients required a second attempt for tracheal intubation, in which indirect (video) laryngoscopy was then performed, representing an 83% second attempt success rate (n = 5; 5.3%). One patient (1.1%) required a third intubation attempt and an alternative device was used to secure the airway (n = 1; Table 1). The most common initial C-L grade view during the first attempt was a 2b (28.7%), which accounted for 36.1% of the 72 patients that were successfully intubated via direct laryngoscopy (n = 26). A noticeable C-L grade view improvement was observed with the use of the McGRATH™ MAC using the indirect view. Thus, the most common initial indirect C-L grade view during the first attempt was a 1 (54.3%), which accounted for 65.3% of the 72 patients that were successfully intubated via direct laryngoscopy (n = 47). ConclusionThe McGRATH™ MAC is a versatile laryngoscope that allows both direct and indirect (video) laryngoscopy to be performed, simultaneously if needed, with a favorable chance of successful intubation during the first attempt. VAL with the McGRATH™ MAC exhibited an enhanced glottic view and served as a successful rescue airway device during inadequate glottic visualization and/or unsuccessful tracheal intubation, after failing with the same device when direct laryngoscopy was performed.

Anthropometric Specific Features of Patients with Cancer of Prostate

The article presents our own data on the results of anthropometry in 42 patients with prostate cancer, the average age is 69.3 ± 2.6 years. The most common somatotype is the gynaecomorphics. However, among the male population, mesomorphs predominate. Excess nutrition and obesity do not affect the risk of developing prostate cancer. Determination of patient somatotype by Rees-Eysenck index showed that men of pyknic type suffering from PC made up 41.5%, normosthenic type -39%, asthenic type - 19.5%. When comparing the frequency of patient somatotypes and men of the population there is a striking contrast.

Acitretin Use in Dermatology.

Acitretin has been used for the treatment of severe psoriasis for over 20 years. The current project was conceived to optimise patient care by recognising the role acitretin can play in the treatment of patients with psoriasis and those with other disorders of keratinisation. A literature review was conducted to explore the role of acitretin and to assess its value for dermatologic disorders other than severe psoriasis. A panel of Canadian dermatologists developed a clinical pathway using a case-based approach, focusing on specific patient features. The clinical pathway covers plaque psoriasis with hyperkeratotic plantar disease, palmoplantar pustulosis, hyperkeratotic hand dermatitis, lichen planus, lamellar ichthyosis, and hidradenitis suppurativa. The recommendations in our clinical pathway reflect the current use of acitretin in Canada for severe psoriasis and other disorders of keratinisation.

Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study

PurposeWe report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy. Methods240 patients received APBI (4Gy, twice daily; total dose 32Gy). ResultsMedian follow-up was 96months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6–4.3) and 6.6% (95%CI: 2.7–12.9). Regional recurrences developed in 5 patients (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of 32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis (p=0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value 0.72). ConclusionsAPBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base.

Hypopituitarism due to mutation in the PROP1 gene in association with the 47,XYY karyotype and autosomal dominant atrioventricular septal defect: two case reports

Application of genetic analysis in clinical practice enables identifying a combination of two rare diseases in one patient. We report two cases of patients with hypopituitarism due to PROP1 gene mutations in combination with the 47,XYY karyotype (case 1) and autosomal dominant partial atrioventricular septal defect (case 2). These clinical cases clearly demonstrate that several rare diseases can be present in one patient. The morphology of the pituitary gland has specific features in patients with a PROP1 gene mutation: signal inversion on T1- and T2-weighted images, as well as changes in size of the pituitary gland over time. In case of short stature, the hormonal evidence of secondary hypopituitarism, low IGF-1 levels, and specific morphological features observed in MRI images, we recommended carrying out molecular genetic analysis of the PROP1 gene without conducting growth hormone stimulation test.

Pisa syndrome in Parkinson's disease: An integrated approach from pathophysiology to management.

Pisa syndrome was first described in 1972 in patients treated with neuroleptics. Since 2003, when it was first reported in patients with Parkinson's disease (PD), Pisa syndrome has progressively drawn the attention of clinicians and researchers. Although emerging evidence has partially clarified its prevalence and pathophysiology, the current debate revolves around diagnostic criteria and assessment and the effectiveness of pharmacological, surgical, and rehabilitative approaches. Contrary to initial thought, Pisa syndrome is common among PD patients, with an estimated prevalence of 8.8% according to a large survey. Furthermore, it is associated with the following specific patient features: more severe motor phenotype, ongoing combined pharmacological treatment with levodopa and dopamine agonists, gait disorders, and such comorbidities as osteoporosis and arthrosis. The present literature on treatment outcomes is scant, and the uneven effectiveness of specific treatments has produced conflicting results. This might be because of the limited knowledge of Pisa syndrome pathophysiology and its variable clinical presentation, which further complicates designing randomized clinical trials on this condition. However, because some forms of Pisa syndrome are potentially reversible, there is growing consensus on the importance of its early recognition and the importance of pharmacological adjustment and rehabilitation. © 2016 International Parkinson and Movement Disorder Society.