From chemotherapy to targeted treatment

Today, melanoma is considered as a spectrum of melanocytic malignancies that can be characterized by clinical and molecular features, including targetable mutations in several kinases. The successful development of therapies, targeting mutated BRaF (v-raf murine sarcoma viral oncogene homolog B1) or c-KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog), has resulted in new treatment options including vemurafenib, imatinib and mitogen-activated protein kinase inhibitors. These molecules are selected if the respective mutation is present. after this first progress in the treatment of advanced melanoma, there is expectation that combinations of kinase inhibitor will additionally improve the overall survival rates and progression-free survival in advanced melanom

Early Physical Therapist Interventions for Patients With COVID-19 in the Acute Care Hospital: A Case Report Series.

The aim of this case series was to describe the experience of Swiss physical therapists in the treatment of patients with COVID-19 during their acute care hospital stay and to discuss challenges and potential strategies in the clinical management of these patients. We report 11 cases of patients with COVID-19 from 5 Swiss hospitals that illustrate the various indications for physical therapy, clinical challenges, potential treatment methods, and short-term response to treatment. Physical therapists actively treated patients with COVID-19 on wards and in the intensive care unit. Interventions ranged from patient education, to prone positioning, to early mobilization and respiratory therapy. Patients were often unstable with quick exacerbation of symptoms and a slow and fluctuant recovery. Additionally, many patients who were critically ill developed severe weakness, postextubation dysphagia, weaning failure, or presented with anxiety or delirium. In this setting, physical therapy was challenging and required specialized and individualized therapeutic strategies. Most patients adopted the proposed treatment strategies, and lung function and physical strength improved over time. Physical therapists clearly have a role in the COVID-19 pandemic. Based on our experience in Switzerland, we recommend that physical therapists routinely screen and assess patients for respiratory symptoms and exercise tolerance on acute wards. Treatment of patients who are critically ill should start as soon as possible to limit further sequelae. More research is needed for awake prone positioning and early breathing exercises as well as post-COVID rehabilitation. To date, there are few data on the physical therapist management of patients with COVID-19. This article is among the first to describe the role of physical therapists in the complex pandemic environment and to describe the potential treatment strategies for countering the various challenges in the treatment of these patients

Predictive validity of the Chelsea Critical Care Physical Assessment tool (CPAx) in critically ill, mechanically ventilated adults: a prospective clinimetric study

Purpose To investigate the predictive validity of the Chelsea Critical Care Physical Assessment tool (CPAx) at intensive care unit (ICU) discharge in critically ill adults for their 90-day outcomes. Materials and methods This prospective clinimetric study investigated four theory-driven, a-priori hypotheses in critically ill adults recruited within 72-144 h of mechanical ventilation. The primary hypothesis was a moderate accuracy (AUROC = 0.750) in predicting residence at home within 90 days. Secondary hypotheses included discrimination between hospital discharge destinations, correlation with subsequent health-related quality of life and length of ICU stay. Results We observed a good accuracy (AUROC = 0.778) of the CPAx at ICU discharge in predicting a return to home within 90 days. The CPAx score significantly increased between the discharge groups "undesirable" <= "rehabilitation" <= "home" (p < 0.001), but was not associated with 90-day health-related quality of life (physical: r = 0.261, mental: r = 0.193). Measured at baseline, CPAx scores correlated as expected with length of ICU stay (r = -0.443). Conclusions The CPAx at ICU discharge had a good predictive validity in projecting residence at home within 90 days and general discharge destinations. The CPAx might therefore have clinical value in prediction, though it does not seem useful to predict subsequent health-related quality of life

Early Rehabilitation Interventions and Physical Therapy in Adults Who Were Critically Ill With COVID-19 Pneumonia: A Retrospective Observational Study.

OBJECTIVE The primary objective of this observational study was to analyze the time to the first edge-of-bed (EOB) mobilization in adults who were critically ill with severe versus non-severe COVID-19 pneumonia. Secondary objectives included the description of early rehabilitation interventions and physical therapy delivery. METHODS All adults with laboratory-confirmed COVID-19 requiring intensive care unit admission for ≥72 hours were included and divided according to their lowest PaO2/FiO2 ratio into severe (≤100 mmHg) or non-severe (>100 mmHg) COVID-19 pneumonia. Early rehabilitation interventions consisted of in-bed activities, EOB or out-of-bed mobilizations, standing, and walking. The Kaplan-Meier estimate and logistic regression were used to investigate the primary outcome time-to-EOB and factors associated with delayed mobilization. RESULTS Among the 168 patients included in the study (mean age = 63 y [SD = 12 y]; Sequential Organ Failure Assessment = 11 [interquartile range = 9-14]), 77 (46%) were classified as non-severe, and 91 (54%) were classified as severe COVID-19 pneumonia. Median time-to-EOB was 3.9 days (95% CI = 2.3-5.5) with significant differences between subgroups (non-severe = 2.5 days [95% CI = 1.8-3.5]; severe = 7.2 days [95% CI = 5.7-8.8]). Extracorporeal membrane oxygenation use and high Sequential Organ Failure Assessment scores (adjusted effect = 13.7 days [95% CI = 10.1-17.4] and 0.3 days [95% CI = 0.1-0.6]) were significantly associated with delayed EOB mobilization. Physical therapy started within a median of 1.0 days (95% CI = 0.9-1.2) without subgroup differences. CONCLUSION This study shows that early rehabilitation and physical therapy within the recommended 72 hours during the COVID-19 pandemic could be maintained regardless of disease severity. In this cohort, the median time-to-EOB was fewer than 4 days, with disease severity and advanced organ support significantly delaying the time-to-EOB. IMPACT Early rehabilitation in the intensive care unit could be sustained in adults who are critically ill with COVID-19 pneumonia and can be implemented with existing protocols. Screening based on the PaO2/FiO2 ratio might reveal patients at risk and increased need for physical therapy

Melanomtherapie - ein Paradigma für die «personalized medicine»

Progress in molecular biology has facilitated a new classification for melanoma. Melanomas today are considered as a heterogeneous group of tumors. The different subtypes are characterized by specific genetic alterations, including mutations in kinase, such as B-RAF or c-kit. New medications like vemurafenib have been developed and are available for the systemic therapy of advanced melanomas in subpopulations identified by mutation tests. In addition, interferon therapy holds the highest promises to dates in subpopulations of patients characterized by microscopic lymph node involvement and ulceration of the primary tumor. These developments are the first steps resulting in a personalized treatment approach for individuals affected by melanoma

STAndard Reporting of CAries Detection and Diagnostic Studies (STARCARDDS)

AIM: The aim of this paper is to present recommendations from an international workshop which evaluated the methodology and reporting of caries diagnostic studies. As a unique feature, this type of studies is focused on caries lesion detection and assessment, and many of them are carried out in vitro, because of the possibility of histological validation of the whole caries spectrum. This feature is not well covered in the existing reporting STARD guideline within the EQUATOR Network. PARTICIPANTS AND METHODS: An international working group of 13 cariology researchers was formed. The STARD checklist was reviewed and modified for caries detection and diagnosis purposes, in a three-step process of evaluation, consensual modification, and delivery during three 2-day workshops over 18 months. Special attention was paid to reporting requirements of caries studies that solely focus on reliability. RESULTS: The STARD checklist was modified in 14/30 items, with an emphasis on issues of sample selection (tooth selection in in vitro studies), blinding, and detailed reporting of results. CONCLUSION: Following STARCARDDS (STAndard Reporting of CAries Detection and Diagnostic Studies) is expected to result in complete reporting of study design and methodology in future caries diagnosis and detection experiments both in vivo and in vitro, thus allowing for better comparability of studies and higher quality of systematic reviews. CLINICAL RELEVANCE: Standardization of caries diagnostic studies leads to a better comparability among future studies, both in vivo and in vitro

Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sézary syndrome)

BACKGROUND Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of deoxyguanosine triphosphate (dGTP) in T and B cells, resulting in apoptosis. Forodesine has demonstrated impressive antitumor activity in early phase clinical trials in cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS In this phase II study, patients with CTCL who had already failed three or more systemic therapies were recruited. We investigated the response rate, safety and tolerability of oral forodesine treatment in subjects with cutaneous manifestations of CTCL, stages IB, IIA, IIB, III and IVA. The safety population encompassing all stages was used for analysis of accountability, demographics and safety. The efficacy population differed from the safety population by exclusion of stage IB and IIA patients. RESULTS All 144 patients had performance status 0-2. The median duration of CTCL from diagnosis was 53 months (5-516 months). The median number of pretreatments was 4 (range: 3-15). No complete remissions were observed. In the efficacy group of patients, 11% achieved partial remission and 50% had stable disease. The median time to response was 56 days and the median duration of response was 191 days. A total of 96% of all treated patients reported one or more adverse events (AEs) and 33% reported a serious AE. The majority of AEs were classified as mild or moderate in severity. The most commonly reported AEs (>10%) were peripheral edema, fatigue, insomnia, pruritus, diarrhea, headache and nausea. Overall eight patients died during the study: five due to sepsis and infections, one due to a second malignancy (esophageal cancer), one due to disease progression and one due to liver failure. CONCLUSION Oral forodesine at a dose of 200 mg daily is feasible and shows partial efficacy in this highly selected CTCL population and some durable responses