Systemic sclerosis-associated interstitial lung disease in the EUSTAR database: analysis by region.

OBJECTIVES: The prevalence and characteristics of SSc-associated interstitial lung disease (SSc-ILD) vary between geographical regions worldwide. The objectives of this study were to explore the differences in terms of prevalence, phenotype, treatment and prognosis in patients with SSc-ILD from predetermined geographical regions in the EUSTAR database. MATERIAL AND METHODS: Patients were clustered into seven geographical regions. Clinical characteristics and survival of patients with SSc-ILD were compared among these pre-determined regions. RESULTS: For baseline analyses, 9260 SSc patients were included, with 6732 for survival analyses. The prevalence of SSc-ILD in the overall population was 50.2%, ranging from 44.0% in 'Western Europe and Nordic countries' to 67.5% in 'Eastern European, Russia and Baltic countries'. In all regions, anti-topoisomerase antibodies were associated with SSc-ILD. Management also significantly differed; mycophenolate mofetil was prescribed at baseline in 31.6% of patients with SSc-ILD in 'America (North and South)' and 31.7% in 'Middle East' but only 4.3% in 'Asia and Oceania' (P <0.0001). Patients from 'America (North and South)' and 'Middle East' had the highest survival rate at the end of follow-up (85.8% and 85.2%, respectively). CONCLUSIONS: Our study highlights key differences among regions in terms of clinical presentation and prognosis of SSc-ILD. This work also demonstrates that the management of SSc-ILD is highly variable among the different regions considered, suggesting that efforts are still needed for the standardization of medical practice in the treatment of this disease.

Body mass index and immune-related adverse events in patients on immune checkpoint inhibitor therapies: a systematic review and meta-analysis.

BACKGROUND: As a result of the growing use of immune checkpoint inhibitors (ICIs) for treating malignancy, immune-related adverse events (irAEs) have been increasingly reported. Higher body mass index (BMI) has been highlighted as a potential risk factor for the development of irAEs. However, there are no meta-analyses summarizing the association between BMI and irAEs in patients on ICI therapies. METHODS: PubMed, MEDLINE, EMBASE, Cochrane and grey literature were searched up to January 2020. Odds ratios (ORs) 95% and confidence intervals (CIs) were summarized using the random-effects model. Heterogeneity test, subgroup and sensitivity analyses were conducted. The protocol was registered on PROSPERO (number registration: CRD42020168790). RESULTS: Five studies (n = 1937) met eligibility criteria for inclusion. Being overweight or obese was associated with an increased odds of developing irAEs (OR 2.62, 95% CI 1.70-4.03, P ≤ 0.00001, I2 = 53%). In subgroup analyses, higher BMI was associated with irAEs in patients using anti-CTLA-4 single agents or in combination with anti-PD-1/PD-L1 (OR 1.87, 95% CI 1.17-2.98, P = 0.009, I2 = 0%) and in patients using anti-PD-1/PD-L1 (OR 3.22, 95% CI 2.06-5.01, P = 0.00001, I2 = 32%) monotherapy. The increased odds of irAEs in patients with higher BMI was comparable (test for subgroup differences, P = 0.72, I2 = 0%) between studies with adjusted OR (OR 2.21, 95% CI 1.44-3.38, P = 0.0003, I2 = 4%) and unadjusted OR (OR 2.65, 95% CI 1.08-6.50, P = 0.03, I2 = 66%). CONCLUSION: Our meta-analysis provides evidence of a relationship between higher BMI (overweight-obesity) and increased risk of irAEs in patients on ICI therapies. Further research is needed to strengthen this association.

Sarcopenia and the risk of adverse events in patients treated with immune checkpoint inhibitors: a systematic review.

BACKGROUND: Sarcopenia has been associated with negative clinical outcomes in cancer patients, particularly response to treatment and survival. The exponential growth in the use of immune checkpoint inhibitors (ICIs) has led to an increase in the reporting of both adverse events in general (AEs) and immune-related adverse events (irAEs), which are unintended immune-related phenomenon that take place as a result of checkpoint blockade. However, there are no systematic reviews evaluating the relationship between sarcopenia and the risk of developing AEs and irAEs in cancer patients on ICI therapies. METHODS: PubMed, MEDLINE, Embase, Cochrane and grey literature, repositories, websites Open Grey, Google Scholar, and abstracts of major international congresses were searched up to April 2020 for observational studies on sarcopenia and both AEs and irAEs in patients treated with ICIs. Study quality was assessed with The Newcastle-Ottawa quality assessment scale. PROSPERO registration number: CRD42020197178. RESULTS: One hundred and thirteen discrete articles were identified. Seven studies were included after evaluation of the eligibility criteria. Important sources of heterogeneity including the specific cut-points defining sarcopenia, sample size, inclusion and exclusion criteria, treatment regimen, and baseline demographics were evaluated and accounted for accordingly. CONCLUSION: Most of the included studies showed an increased risk of AEs with use of ICIs in cancer patients with sarcopenia, and in the majority of these, the increase was statistically significant. Due to the small number of available studies and the expanding use of ICIs, additional research is warranted.

The Utility of 68Ga-PSMA PET/CT in Decisions Regarding Administering Salvage Radiotherapy to Men with Prostate Cancer.

BACKGROUND: Numerous papers have described 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)'s sensitivity in identifying prostate cancer (PCa) recurrence. This study aimed to characterize the role of 68Ga-PSMA PET/CT in deciding to re-irradiate pelvic structures. METHODS: 68Ga-PSMA PET/CT scans performed at Sheba Medical Center over seven years in 113 men were reviewed. All had undergone radiation to the prostate (70, 61.9%) or post-radical prostatectomy radiation to the prostate fossa (PF) (43, 48.1%), and had local or oligometastatic PCa recurrence and received salvage radiotherapy (SRT) based on PET/CT findings. RESULTS: Mean age was 70.7 years. The mean grade group was 2.9; the mean prostate-specific antigen was 9.0. The 68Ga-PSMA PET/CT positive findings included: 37 (32.7%) in the prostate, 23 (20.4%) in seminal vesicles, 7 (6.2%) in the PF, and 3 (2.7%) in the seminal vesicle fossa. The mean standardized uptake value was 10.6 ± 10.2 (range: 1.4-61.6); the mean lesion size was 1.8 ± 3.5 mm (range: 0.5-5.1). SRT was directed toward the prostate and seminal vesicles in 48 (42.5%), PF in 18 (15.9%), and intrapelvic lymph node and bone in 47 (41.6%). Toxicities were mostly mild to moderate. CONCLUSION: 68Ga-PSMA PET/CT-identified relapse with targeted SRT was well-tolerated and may result in less onerous treatments.

Effectiveness and safety of immune checkpoint inhibitors in combination with palliative radiotherapy in advanced melanoma: A systematic review.

BACKGROUND: Radiotherapy is frequently added to immune checkpoint inhibitors (ICI) when treating melanoma. We sought to describe the efficacy of combination ICI and palliative radiotherapy (pRT) and assess safety, focusing on immune related adverse events (irAE). METHODS: A systematic search for studies investigating the combination of pRT and ICI was conducted. RESULTS: Five hundred-two articles were identified; nine met inclusion criteria. Improvements in objective response rate (p = 0.02), complete response (p = 0.04), and one-year local control (p < 0.005) were demonstrated when pRT was added to ICI. While some studies revealed improved overall and progression free survival, findings were mixed. No significant increases in adverse events or irAE were seen with the combined treatment compared with ICI alone. CONCLUSION: The included studies revealed that the addition of pRT to ICI is effective and safe in patients with advanced melanoma. Measures of survival varied. More studies are warranted to identify optimal conditions for combination treatment.

The Utility of 18FDG-PET/CT in Diagnosing Fever of Unknown Origin: The Experience of a Large Tertiary Medical Center.

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18-93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.

Penile secondary lesions: a rare entity detected by PET/CT.

While penile metastases are rare, PET/CT has facilitated their detection. We aimed to describe penile secondary lesions (PSL) identified by PET/CT. We reviewed 18F-FDG and Ga68-PSMA PET/CT records performed in a single center during May 2012-March 2020, for PSL. Of 16,774 18F-FDG and 1,963 Ga68-PSMA-PET scans, PSL were found in 24(0.13%) men with a mean age of 74. PSMA detected PSL in 12 with prostate cancer; FDG identified PSL in 4 with lymphoma, 3 with colorectal cancer, 2 with lung cancer, and one each with bladder cancer, pelvic sarcoma, and leukemia. Mean SUVmax of PSL was 7.9 ± 4.2 with focal uptake in 13(54%). Mean lesion size was 16.5 ± 6.8 mm; 8 at the penile root, 4 along the shaft, and 1 at the glans. CT detected loss of the penile texture in 15(63%). PSL were observed only during relapse or follow-up of disseminated disease. Among those with prostate cancer, PSA varied widely. Fifteen (62.5%) died, at a mean 13.3 ± 15.9 months following PSL demonstration, nine had non-prostate malignancies. PET/CT identified and characterized PSL in a fraction of cancer patients, most commonly those with prostate cancer. PSL universally surfaced in advanced disease, and signaled high mortality, especially in non-prostate cancers.

Characterization of hyperglycemia in patients receiving immune checkpoint inhibitors: Beyond autoimmune insulin-dependent diabetes.

AIMS: Immune-mediated beta cell destruction is known to cause hyperglycemia in patients receiving immune checkpoint inhibitor (ICI) cancer therapy. However, it is uncommon, and little is known about the full spectrum of hyperglycemia in patients receiving ICIs. We aimed to characterize the prevalence and factors associated with hyperglycemia in patients treated with ICIs. METHODS: We retrospectively analyzed patients receiving ICIs at an NCI-designated Cancer Center. We assessed the proportion of patients with new onset hyperglycemia (random glucose >11.1 mmol/L) after starting ICIs and used logistic regression to determine hyperglycemia predictors in patients without known diabetes. RESULTS: Of 411 patients, 385 had post-ICI glucose data. 105 (27%) had hyperglycemia. Of this group, 29 (28%) had new onset hyperglycemia, 19 of whom had glucocorticoid-associated hyperglycemia. The remaining 10 had unexplained hyperglycemia and none had known autoimmune diabetes. Among patients without known diabetes, race/ethnicity, obesity, and pre-ICI hyperglycemia were significantly associated with hyperglycemia after starting ICIs. CONCLUSIONS: We found that new hyperglycemia in patients receiving ICIs was most commonly related to glucocorticoids. A small patient subset had new unexplained hyperglycemia, suggesting ICIs might have a role in promoting hyperglycemia. Recognizing factors associated with hyperglycemia in this population is crucial for appropriate management.

The utility of PET/CT in large vessel vasculitis.

18F-FDG PET/CT occupies a growing role in the diagnosis of large vessel vasculitis (LVV), illustrating enhanced uptake in the lining of large vessels. A retrospective single center study was conducted of patients who underwent 18F-FDG PET/CT scans between 2009 and 2019 at Sheba Medical Center, Israel. The imaging results were analyzed for evidence of LVV. We reviewed the PET/CT scans of 126 patients and identified 57 studies that either showed evidence of active LVV or that had been performed in patients previously treated for systemic vasculitis. In 6 patients with fevers of unknown origin and elevated inflammatory markers, PET/CT revealed LVV. Six of 13 patients previously treated for systemic vasculitis demonstrated persistent large vessel uptake. LVV was identified in 8 patients with other autoimmune diseases, and in 4 diagnosed with infectious aortitis. In 26 patients who underwent malignancy surveillance, PET/CT revealed more localized large vessel wall inflammation. Our results illustrate that PET/CT may identify large vessel wall inflammation in patients with a suspicion of LVV, and incidentally in patients who undergo malignancy surveillance. PET/CT may also help delineate the presence and extent of vessel inflammation in patients with LVV and in those with other autoimmune diseases.

Medical education and research during the COVID-19 pandemic: How to meet the challenges posed / Educación e investigación médica durante la pandemia de COVID-19: cómo enfrentar los desafíos planteados / Educação médica e pesquisa durante a pandemia COVID-19: como enfrentar os desafios colocados

The COVID-19 pandemic has prompted numerous challenges for the field of education, particularly medical education and health-related research. However, these obstacles are also an opportunity to advance this academic-medical sphere with the increased introduction of information technologies and the creation of strategies that focus on quality improvement. Previous research has highlighted the importance of adapting both clinical practice and medical education within the context of the pandemic (1). As COVID-19 continues to surge across the globe, the gaps in medical education and research grow and they must be met urgently with a creative approach toward making the available technology accessible and relevant. https://doi.org/10.29375/01237047.4019

La pandemia de COVID-19 ha generado numerosos desafíos para el campo de la educación, en particular el médico. educación e investigación relacionada con la salud. Sin embargo, estos obstáculos también son una oportunidad para avanzar en este ámbito académico-médico con la mayor introducción de tecnologías de la información y la creación de estrategias que se centran en la mejora de la calidad. Investigaciones anteriores han destacado la importancia de adaptar tanto la práctica clínica como la educación médica en el contexto de la pandemia (1). Mientras continúa COVID-19 aumenten en todo el mundo, las brechas en la educación e investigación médicas crecen y deben abordarse urgentemente con un enfoque creativo para hacer que la tecnología disponible sea accesible y relevante. https://doi.org/10.29375/01237047.4019

A pandemia COVID-19 criou inúmeros desafios para o campo da educação, especialmente o médico. educação e pesquisas relacionadas à saúde. No entanto, esses obstáculos são também uma oportunidade para avançar neste campo médico-acadêmico com a maior introdução das tecnologias de informação e a criação de estratégias que visem a melhoria da qualidade. Pesquisas anteriores destacaram a importância de adaptar a prática clínica e a educação médica no contexto da pandemia (1). À medida que o COVID-19 continua a aumentar em todo o mundo, as lacunas na educação médica e na pesquisa estão crescendo e devem ser abordadas com urgência com uma abordagem criativa para tornar a tecnologia disponível acessível e relevante. https://doi.org/10.29375/01237047.4019