Cancers of Unknown Primary Origin: Real-World Clinical Outcomes and Genomic Analysis at the European Institute of Oncology.

BACKGROUND: Cancer of unknown primary origin (CUP) poses a significant challenge due to poor clinical outcomes and limited treatment options. As such, further definition of clinicopathological factors and genomic profile to better adapt treatment strategies is required. METHODS: Medical records were interrogated to retrospectively include CUP with available clinical and genomics data at the European Institute of Oncology. Next-generation sequencing (NGS) included targeted panels. Statistical analyses were conducted with R Software 4.2.2. RESULTS: A total of 44 patients were included. With a median follow-up of 39.46 months (interquartile range [IQR] 35.98-47.41 months), median PFS (mPFS) to first-line regimen was 3.98 months (95% CI 3.22-5.98), with a clinical benefit rate of 26% (95% CI 14%-49%), and disease control rate (DCR) limited to 48.28%. Most patients (26 of 31, 83.87%) received platinum-doublet chemotherapy, with no statistically significant difference between first-line treatment regimens. Median OS (mOS) was 18.8 months (95% CI 12.3-39.9), with a 12-month OS rate of 66% (95% CI 50%-85%). All patients received comprehensive genomic profiling (CGP). For 11 patients, NGS was unsuccessful due to low sample quantity and/or quality. For the remaining, TP53 (n = 16, 48%) and KRAS (n = 10, 30%) represented the most altered (alt) genes. No microsatellite instability was observed (0 of 28), while 6 of 28 (21.43%) tumors carried high TMB (≥10 mutation per megabase). Eight of 33 tumors (24.2%) displayed at least one actionable alteration with potential clinical benefit according to ESCAT. Only 2 of them received targeted therapy matched to genomic alterations, with a combined mPFS of 2.63 months (95% CI 1.84-not evaluable) as third-line regimens. Six patients received anti-PD1/PD-L1 therapy, showing a meaningful mPFS of 13 months (95% CI 2.04-not evaluable). CONCLUSION: CUP exhibits poor prognosis with limited benefits from standard treatment regimens. A significant proportion of CUPs carry actionable alterations, underscoring the importance of genomic profiling to gather additional treatment opportunities. In addition, immunotherapy might represent a valuable treatment option for a subset of CUP. Finally, accurate definition of sequencing methods and platforms is crucial to overcome NGS failures.

Prevalence of people living with multidrug-resistant HIV and limited treatment options in Spain.

OBJECTIVES: Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) with multidrug resistance (MDR; confirmed resistance to three or more [or resistance to two or more plus contraindication to one or more] core ART classes) and limited treatment options (LTOs) in Spain. METHODS: This was an observational, retrospective, multicentre, cross-sectional chart review study undertaken in five reference Spanish centres. Participants were people with HIV on ART with MDR and LTOs (detectable viral load [HIV-RNA >200 copies/mL], treatment-limiting drug-drug interaction [DDI], or intolerance precluding the use of one or more ART classes). Prevalence, demographic/clinical characteristics, and treatment options were assessed. Logistic regression analyses were used to identify MDR-associated variables. RESULTS: Of 14 955 screened people with HIV, 69 (0.46%) presented with MDR and 23 (0.15%) had LTOs. The population analysed was 73.9% male with a median age of 54.0 years; the median time since HIV diagnosis was 26.5 years, and median CD4+ cell count was 511.0 cells/µL. The only factor significantly associated with MDR (univariate analysis) was CD4+ cell count. Injection drug use was the most common transmission route. Comorbidities (mainly endocrine and cardiovascular disorders; 34.8% affecting HIV management) and concomitant treatments were frequent. No recent opportunistic infections were reported. Patients had been exposed to the following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease inhibitors (95.6%), non-nucleoside analogue reverse transcriptase inhibitors (87.0%), and integrase strand transfer inhibitors (82.6%). The available fully active drugs were dolutegravir (39.1%), bictegravir (30.4%), and raltegravir (21.7%). CONCLUSIONS: The prevalence of people with HIV with MDR and LTOs in Spain is very low, with approximately half of those studied not exhibiting virological suppression. Low CD4+ cell counts were associated with MDR. These findings may help address the impact and treatment needs of these patients and prevent clinical progression and transmission of MDR HIV.

Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts.

AIMS: Treatment options for advanced urothelial carcinoma (aUC) rapidly evolved: besides immunomodulative therapeutic options and inhibitors targeting Fibroblast growth factor receptor (FGFR) alterations, two new antibody-drug conjugates (ADC), sacituzumab govitecan (SG) and enfortumab vedotin (EV), have been approved. However, little is known about the associations of specific aUC properties and the surface target expression of TROP2 and NECTIN-4. Our aim was to characterize associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 protein and gene expression with morphomolecular and clinicopathological characteristics of aUC in two large independent cohorts. METHODS AND RESULTS: The TCGA BLCA (n = 405) and the CCC-EMN (n = 247) cohorts were retrospectively analysed. TROP2/TACSTD2 and NECTIN-4/NECTIN-4 are highly expressed at the protein and transcript level in aUC, and their expression status did not correlate with patient survival in both cohorts. NECTIN-4/NECTIN-4 expression was higher in luminal tumours and reduced in squamous aUCs. NECTIN-4 was negative in 10.6% of samples, and 18.4% of samples had low expression (H-score <15). The TROP2 negativity rate amounted to 6.5%. TACSTD2 and NECTIN-4 expression was reduced in neuroendocrine-like and/or protein-based double-negative tumours. TROP2- and NECTIN-4-negative tumours included one sarcomatoid and four neuroendocrine aUC. FGFR3 alterations and PD-L1 expression on tumour and immune cells did not associate with TROP2 or NECTIN-4 expression. CONCLUSIONS: TACSTD2/TROP2 and NECTIN-4/NECTIN-4 are widely expressed in aUC, independent of FGFR3 alterations or PD-L1 expression, thus representing a suitable target for ADC treatment in the majority of aUC. The expression loss was associated with aggressive morphomolecular aUC subtypes, i.e. neuroendocrine(-like) and sarcomatoid aUC.

Understanding depression with amyotrophic lateral sclerosis: a short assessment of facts and perceptions.

Depression with an average prevalence of 25-40% is a serious condition in amyotrophic lateral sclerosis (ALS) that can impact quality of life and survival of patients and caregiver burden, yet the underlying neurobiology is poorly understood. Preexisting depression has been associated with a higher risk of developing ALS, while people with ALS have a significantly higher risk of developing depression that can cause multiple complications. Depression may be a prodromal or subclinical symptom prior to motor involvement, although its relations with disease progression and impairment of quality of life are under discussion. Unfortunately, there are no studies existing that explore the pathogenic mechanisms of depression associated with the basic neurodegenerative process, and no specific neuroimaging data or postmortem findings for the combination of ALS and depression are currently available. Experience from other neurodegenerative processes suggests that depressive symptoms in ALS may be the consequence of cortical thinning in prefrontal regions and other cortex areas, disruption of mood-related brain networks, dysfunction of neurotransmitter systems, changing cortisol levels and other, hitherto unknown mechanisms. Treatment of both ALS and depression is a multidisciplinary task, depression generally being treated with a combination of antidepressant medication, physiotherapy, psychological and other interventions, while electroconvulsive therapy and deep brain stimulation might not be indicated in the majority of patients in view of their poor prognosis. Since compared to depression in other neurodegenerative diseases, our knowledge of its molecular basis in ALS is missing, multidisciplinary clinicopathological studies to elucidate the pathomechanism of depression in motor system disorders including ALS are urgently warranted.

The enigma of depression in corticobasal degeneration, a frequent but poorly understood co-morbidity.

Depression is one of the most frequent neuropsychiatric symptoms in corticobasal degeneration (CBD), a rare, sporadic, and late-onset progressive neurodegenerative disorder of unknown etiology. It is clinically characterized by a levodopa-poorly responsible akinetic-rigid syndrome, apraxia, limb dystonia, cognitive, mood, behavioral, and language disorders. This 4-repeat (4R) tauopathy is morphologically featured by asymmetric frontoparietal atrophy, neuronal loss, and gliosis in cortex and subcortex including substantia nigra, ballooned/achromatic neurons with filamentous 4R tau aggregates in cortex and striatum, widespread thread-like structures, pathognomonic "astroglial plaques", "tufted astrocytes", and numerous "coiled bodies" (in astrocytes and oligodendroglia) in cerebral white matter. CBD is non-specific, as pathologically proven cases include several clinical phenotypes. Pubmed and Google Scholar were systematically analyzed until October 2023, with focus on the prevalence, clinical manifestation, neuroimaging data, and treatment options of depression in CBD. Its prevalence is about 30-40% which is more frequent than in most other atypical parkinsonian syndromes. Depression usually does not correlate with motor and other clinical parameters, suggesting different pathophysiological mechanisms. Asymmetric atrophy and hypometabolism of frontoparietal cortical areas are associated with disruption of fronto-subcortical circuits, nigrostriatal dopaminergic, and cholinergic deficiency. Since no specific neuroimaging, neuropathological, or biomarker studies of depression in CBD are available, its pathobiological mechanisms and pathogenesis are poorly understood. Antidepressive therapy may be useful, but is often poorly tolerated. Depression in CBD, like in other parkinsonian syndromes, may be related to multi-regional patterns of cerebral disturbances and complex pathogenic mechanisms that deserve further elucidation as a basis for early diagnosis and adequate treatment to improve the quality of life in this fatal disease.

Depression and anxiety in multiple sclerosis. Review of a fatal combination.

Depression and anxiety are the most frequent neuropsychiatric symptoms of multiple sclerosis (MS), an autoimmune-mediated demyelinating neurodegenerative disease. Their prevalence is 25-65% and 20-54%, respectively, often associated with chronic fatigue and cognitive impairment, but usually not correlated with motor and other deficits, suggesting different pathophysiological mechanisms. Both disorders often arise before MS diagnosis, lead to faster disability and impair the quality of life. Risk factors are (young) age, genetic and family history burden. While no specific neuropathological data for depression (and anxiety) in MS are available, modern neuroimaging studies showed bilateral fronto-temporal, subcortical and limbic atrophies, microstructural white matter lesions and disruption of frontoparietal, limbic and neuroendocrine networks. The pathogenesis of both depression and anxiety in MS is related to shared mechanisms including oxidative stress, mitochondrial dysfunction, neuroinflammation and neuroendocrine mechanisms inducing complex functional and structural brain lesions, but they are also influenced by social and other factors. Unfortunately, MS patients with anxiety, major depression or suicidal thoughts are often underassessed and undertreated. Current treatment, in addition to antidepressant therapy include transcranial magnetic stimulation, cognitive, relaxation, dietary and other healthcare measures that must be individualized. The present state-of- the-art review is based on systematic analysis of PubMed, Google Scholar and Cochrane Library until May 2024, with focus on the prevalence, clinical manifestation, neuroimaging data, immune mechanisms and treatment options. Depression and anxiety in MS, like in many other neuroimmune disorders, are related, among others, to multi-regional patterns of cerebral disturbances and complex pathogenic mechanisms that deserve further elucidation as a basis for early diagnosis and adequate management to improve the quality of life in this disabling disease.

Long-term experiences with high-energy shock wave therapy in the management chronic phase Peyronie's disease using two different electromagnetic lithotripters.

BACKGROUND: Extracorporeal shock wave lithotripsy represents one option for the non-surgical management of Peyronie's disease. Despite promising results, several questions are still pending. We want to present the long-term results of a retrospective study using high-energy extracorporeal shock wave lithotripsy. MATERIAL AND METHODS: We evaluated retrospectively 110 patients treated between 1996 and 2020 at the Department of Urology, SLK Kliniken Heilbronn for chronic phase Peyronie's disease using two electromagnetic lithotripters (Siemens Lithostar Plus Overhead Module, Siemens Lithoskop) applying high-energy shock waves under local anesthesia and sonographic or fluoroscopic control. A standardized questionnaire focused on the change in pain, curvature, sexual function and the need of penile surgery. RESULTS: In 85 of the 110 patients (mean age 54 years) we had sufficient data for evaluation. The median follow-up was 228 (6-288) months. There were no significant complications. Pain reduction was achieved in all patients, 65 (76%) patients were free of pain. Improvement of penile curvature was achieved in 43 patients (51%) ranging from 25% improvement (deflected angle < 30°) to 95% (angle 30-60°). 59 patients (69%) reported problems with sexual intercourse, 40 of those (68%) reported improvement. Only 9 (10.5%) patients underwent surgical correction. We did not observe any significant differences between both electromagnetic devices with stable long-term results. CONCLUSIONS: High-energy shock wave therapy delivered by two standard electromagnetic lithotripters is safe and efficient providing stable long-term results. In cases with significant plaque formation, the concept of high-energy ESWT should be considered in future studies.

Factors influencing older women's decision-making related to treatment of operable breast cancer: A qualitative systematic review.

OBJECTIVE: There is variation in practice in the treatment of older women with breast cancer. International guidelines highlight the importance of patient autonomy in treatment decision-making. The aim of this study is to identify factors which influence decision-making in older women with operable breast cancer, which will enable us to further understand how to support these patients. METHODS: Systematic review in accordance with the PRISMA guidelines was performed to identify factors which influence treatment decision-making in older women with operable breast cancer. Medline, Web of Science and SCOPUS were searched. RESULTS: The search yielded 5840 results; 13 articles met the inclusion criteria and reported on a total of 1118 women. Thematic analysis identified three key themes in which decision-making factors could be categorised. These were healthcare-related factors, patient-related factors and impact of treatment. Healthcare-related factors included communication with clinicians and provision of information. Patient-related factors were age, pre-existing knowledge, preconceptions of breast cancer and treatment, decision-making style and co-morbidities. The impact of treatment considerations included body image and effect on quality of life. Decision-making style was frequently reported; older women did not demonstrate one preferred style. CONCLUSIONS: The findings have highlighted the complex interplay of factors which influence how older women make breast cancer treatment-decisions. Clinicians should have an awareness of the factors highlighted to maximise their ability to provide support and personalised care to older women with breast cancer whilst treatment decisions are made.

Comparison of Old and New Systemic Treatments for Moderate to Severe Atopic Dermatitis.

PURPOSE OF REVIEW: Historically, systemic treatments for atopic dermatitis (AD) primarily consisted of immunosuppressive agents such as corticosteroids and Disease Modifying Antirheumatic Drugs (DMARDS), which provided symptomatic relief but often had long-term adverse effects. Newer treatments have shown significant efficacy with less side effects in clinical trials. This review discusses and compares conventional and newer systemic treatments for AD. RECENT FINDINGS: Newer medications for AD including dupilumab, tralokinumab, lebrikizumab, and oral JAK inhibitors have been shown to be safe and efficacious. High dose cyclosporine and dupilumab were more effective than methotrexate and azathioprine in improving clinical signs of AD. High-dose upadacitinib was shown in another meta-analysis to be most effective in the measured outcomes but had the highest frequency of adverse events. Targeted biologic treatments are increasingly favored over traditional immunosuppressive treatments of AD. Treatment can be individualized based on potency, adverse side effects, mechanism of action, and administration preference. Ongoing research continues to expand treatment options for AD.

Immunotherapy for Brain Tumors: Where We Have Been, and Where Do We Go From Here?

OPINION STATEMENT: Immunotherapy for glioblastoma (GBM) remains an intensive area of investigation. Given the seismic impact of cancer immunotherapy across a range of malignancies, there is optimism that harnessing the power of immunity will influence GBM as well. However, despite several phase 3 studies, there are still no FDA-approved immunotherapies for GBM. Importantly, the field has learned a great deal from the randomized studies to date. Today, we are continuing to better understand the disease-specific features of the microenvironment in GBM-as well as the exploitable antigenic characteristic of the tumor cells themselves-that are informing the next generation of immune-based therapeutic strategies. The coming phase of next-generation immunotherapies is thus poised to bring us closer to treatments that will improve the lives of patients with GBM.

A Prediction Model for the Efficacy of Transvaginal Repair in Patients With Cesarean Scar Defect: An Evidence-Based Proposal for Patient Selection.

STUDY OBJECTIVE: To establish a prediction model to help doctors determine which patients with cesarean scar defect are more suitable for transvaginal repair. DESIGN: Retrospective analysis. SETTING: Xinhua Hospital and Shanghai First Maternity & Infant Hospital between June 2014 and May 2021. PATIENTS: 1015 women who underwent transvaginal repair of cesarean scar defect (CSD). INTERVENTIONS: All enrolled patients underwent CSD repair performed by the same gynecologist and his team. And followed up a clinic visit at 6 months to record their menstruation and measure multiple parameters of the CSD by Magnetic Resonance Imaging. MAIN OUTCOMES AND MEASURES: CSD patients are categorized as optimal healing group when the menstruation duration is no more than 7 days, meanwhile the thickness of residual myometrium is no less than 5.39 mm after vaginal repair. The final nomogram is constructed to predict surgical outcomes based on preoperative variables. RESULTS: The key factors that determine optimal healing are the timing of cesarean section (elective or emergency), menstrual cycle, CSD length, width, depth, and the thickness of the lower uterine segment. With the prediction model, scores are given to each parameter according to the statistics. Total scores range from 0 to 25 points, with a cutoff point of 16.5. When a score is greater than 16.5, the transvaginal repair can achieve optimal healing. Uterine position (anteflexion or retroflexion) and preoperative thickness of residual myometrium are the key factors affecting postoperative thickness of residual myometrium. The width of the CSD and the thickness of the lower uterine segment are the key factors affecting abnormal uterine bleeding symptoms (p < 0.01). CONCLUSIONS: For the first time, we established a prediction model system that may predict the repair effect of CSD and can potentially be useful in future clinical trials to determine which patients are more suitable for surgery or other treatment options.

Case Study: The Weighty Issue of Treatment Options for Obese Dialysis Patients.

Obesity is a complex chronic disease and common comorbidity in kidney failure and is the leading causes of death and disability in this population. Guidelines do not specifically address the preferred weight management option(s) for obesity while on dialysis. Large body size is a limiting factor for consideration of a kidney transplantation. We report on a successful bariatric surgery with a young adult after 5.5 years on dialysis with hope for a future transplant. Success was demonstrated with progressive weight loss without adverse changes in renal clinical markers accompanied by improvements in exercise tolerance and health status thereby improving her suitability for a kidney transplant. Further studies and guidelines are needed to address weight loss options for those with obesity on dialysis and want to lose weight.

[Burnout : Symptoms, diagnostics and treatment approaches]. / Burnout : Symptomatik, Diagnostik und Behandlungsansätze.

Burnout syndrome is characterized by the triad of symptoms exhaustion, mental distance from work activities and a feeling of ineffectiveness. The syndrome is not an independent mental disorder but can be coded in the 10th Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) as a problem related to difficulties in coping with life (Z73) and in ICD-11 as a qualifying diagnosis (QD85). This article discusses the prevalence and comorbidities of burnout syndrome, taking the methodological difficulties in conceptualizing and operationalizing the construct into account. In addition, it provides an overview of available measurement instruments and their validation. Furthermore, it discusses work-related and individual factors in the development of burnout syndrome as well as analysis of the effectiveness of treatment options.

[Non-response to psychotherapy: concepts, problems and referral options]. / Nichtansprechen auf Psychotherapie: Konzepte, Problemstellungen, Zuweisungsoptionen.

AIM: In this paper we review the current literature on the clinical problem that some patients do not achieve response after adequately conducted psychotherapy. We explicate our understanding of nonresponse and treatment resistance including the operational definitions, summarize the theoretical explanations and empirical studies and put forward possible study designs and treatment options. METHODS: Literature search using PubMed and Web of Science. RESULTS: For the domain of psychotherapy, the term treatment resistance does not seem appropriate; instead, we use the more descriptive terms nonresponse and recurrent nonresponse. Generally, this topic is far less represented in psychotherapy than in pharmacotherapy. Controlled switching studies with a switch from pharmacotherapy to psychotherapy are rare and those switching from one psychotherapeutic approach to another are nearly nonexistent. Building on clinical considerations, we propose a flow-chart for clinical decision making after nonresponse in psychotherapy. DISCUSSION: Learning from errors is highly beneficial. This principle should be more consistently followed up in psychotherapy research as well as in supervision and training. Guidelines should include consensual and evidence-based advice on how to deal with nonresponse and recurring nonresponse.

[Migraine and pregnancy : Gender-specific aspects and current knowledge]. / Migräne und Schwangerschaft : Geschlechtsspezifische Aspekte und aktuelles Wissen.

BACKGROUND: Migraine, a frequent and debilitating neurological disease, shows gender-specific differences in prevalence and severity. Pregnancy is associated with numerous unique features in terms of migraine course, treatment options and differential diagnoses. OBJECTIVES: How does pregnancy influence the course of migraine? What are the possible treatment options during pregnancy? Which differential diagnoses should be considered? MATERIAL AND METHODS: Narrative review with summary and discussion of relevant studies and guidelines on migraine in pregnancy. RESULTS: During pregnancy up to three quarters of women experience improvement of their migraine; however, there may be a renewed increase in frequency after childbirth. Choosing an appropriate treatment during pregnancy requires a careful risk-benefit assessment. It is important to consider secondary causes of headache as these can occur more frequently during pregnancy and some can be life-threatening. CONCLUSION: Consideration of specific aspects of migraine in pregnancy is crucial to be able to develop the best possible treatment strategies for affected patients.

Chronic kidney disease in America, Africa, and Asia: Overview of treatment cost and options.

Chronic kidney disease (CKD) is one of the non-infectious diseases that threaten patients' lives on a daily basis. Its prevalence is high, but under-reported by patients and those living with the disease, as it is silent and asymptomatic in the early stages. Kidney disease increases the risk of heart and vascular disease. These problems can manifest themselves slowly, over a long period of time. Early detection and treatment can often prevent chronic kidney disease from worsening. As kidney disease progresses, it can lead to kidney failure, requiring dialysis or a kidney transplant to stay alive. In this narrative review, we will mainly discuss different treatment option costs in different countries and how much they cost healthcare systems in countries in three different continents.

Intracapsular neck of femur fractures secondary to civilian gunshot injuries: an inter- and intra-observer agreement study on classification and treatment using the AO/OTA classification.

PURPOSE: Numerous classification systems have been developed for neck of femur fractures, but none have been tested for reliability in gunshot injuries. Our primary objective was to assess the inter-observer and intra-observer reliability of the AO/OTA classification system when applied to intracapsular neck of femur fractures secondary to low-velocity civilian gunshots wounds (GSWs). Our secondary objective was to test the reliability of the AO/OTA classification system in guiding surgeon treatment choices for these fractures. PATIENTS AND METHODS: Eighteen reviewers (six orthopaedic traumatologists, six general orthopaedic surgeons and six junior orthopaedic fellows) were given a set of 25 plain radiographs and CT scans of femur neck fractures secondary to GSW. For each clinical case, all reviewers selected a classification as well as treatment option from a list of given options. Inter-observer reliability was measured at the initial classification. The exercise was repeated 10-12 weeks later by the same 18 reviewers to test intra-observer reliability. RESULTS: The Fleiss kappa values indicate only slight agreement amongst raters, across all experience levels, for both injury classification and treatment. Intra-observer agreement was fair across all experience levels for both injury classification and treatment. CONCLUSION: The AO/OTA classification showed only slight reliability in classification of gunshot fractures of the femur neck. With only fair reliability, it also failed to guide surgical treatment thus rendering its routine use in daily clinical practice of questionable value.

Resistance to prostate cancer treatments.

A review of the current treatment options for prostate cancer and the formation of resistance to these regimens has been compiled including primary, acquired, and cross-resistance. The diversification of the pathways involved and the escape routes the tumor is utilizing have been addressed. Whereas early stages of tumor can be cured, there is no treatment available after a point of no return has been reached, leaving palliative treatment as the only option. The major reasons for this outcome are the heterogeneity of tumors, both inter- and intra-individually and the nearly endless number of escape routes, which the tumor can select to overcome the effects of treatment. This means that more focus should be applied to the individualization of both diagnosis and therapy of prostate cancer. In addition to current treatment options, novel drugs and ongoing clinical trials have been addressed in this review.

Pathomechanisms of depression in progressive supranuclear palsy.

Depression is one of the most frequent neuropsychiatric symptoms in progressive supranuclear palsy (PSP), a four-repeat tauopathy and most common atypical parkinsonian disorder, but its pathophysiology and pathogenesis are poorly understood. Pubmed/Medline was systematically analyzed until January 2023, with focus on the prevalence, major clinical features, neuroimaging findings and treatment options of depression in PSP. The average prevalence of depression in PSP is around 50%; it does usually not correlate with most other clinical parameters. Depression is associated with multi-regional patterns of morphometric gray matter variations, e.g., reduced thickness of temporo-parieto-occipital cortices, and altered functional orbitofrontal and medial frontal circuits with disturbances of mood-related brain networks. Unfortunately, no specific neuropathological data about depression in PSP are available. Antidepressive and electroconvulsive therapies are effective in improving symptoms; the efficacy of transcranial stimulation needs further confirmation. Depression in PSP is a common symptom, related to multi-regional patterns of cerebral disturbances and complex pathogenic mechanisms that deserve further elucidation as a basis for adequate treatment to improve the quality of life in this fatal disease.

Microbiology and management of respiratory infections in children with tracheostomy.

Tracheostomy-related respiratory infections are common, though the diagnosis and management can be challenging in children. The goal of this review article was to provide an overview of the current knowledge known about recognizing and treating respiratory infections in this population and to emphasize future areas for further research. While several small and retrospective papers attempt to provide information, there remain more questions than answers. We have reviewed ten published articles to understand this topic, bringing to light significant variation in clinical practices across institutions. While identifying the microbiology is important, it is also crucial to recognize when to treat. Differentiating acute infection, chronic infection, and colonization are important features that influence the treatment of lower respiratory tract infection in children with a tracheostomy.