Impact of COVID-19 on the management of patients with Lysosomal Storage Disorders

Lysosomal storage disorders (LSDs) are a group of inborn errors of metabolism (IEM) characterized by multisystemic involvement with multi-organ complications. The recent Covid-19 pandemic had a major impact on the management and treatment of patients with LSDs, who also experienced significant psychological distress following the pandemic. Several experiences described so far demonstrate that telemedicine and home therapy programs are valid tools for the follow-up and care of patients suffering from these complex chronic diseases.

Extreme hyperferritinemia in the pediatric emergency setting: haemophagocytic lymphohistiocytosis, macrophage activation syndrome, sepsis and more

Ferritin plays an important role in modulating inflammation and is a significant marker in some life-threatening pathological conditions. Hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome (MAS), sepsis, and the more recent multisystem inflammatory syndrome in children (MIS-C) share many clinical and laboratory aspects, including the increase in ferritin levels, so that they are considered hyperferritinemic syndromes. In the pediatric emergency setting, the finding of high ferritin levels if associated with fever requires considering these rare syndromes to start a timely therapy.

Why do prostate cancer clinical trials (CT) discontinue prematurely in the era of COVID-19? An analysis of 559 CT from ClinicalTrial.gov

Background: The COVID-19 pandemic (C19P) is producing several detrimental effects on cancer care globally. CT play a decisive role to provide high quality literature evidence and “poor accrual” is the most common reason for their early discontinuation (ED). At our best knowledge, no data are available on ED of prostate cancer CT after the beginning of C19P. Material and methods: ClinicalTrial.gov was queried for terminated (T), withdrawn (W) and suspended (S) CT for the following terms: “cancer”, “neoplasm” and “tumor”. CT not related on prostate cancer were excluded. The search was made for all the CT available from the inception to 26th February 2021, without any restrictions. The following characteristics were extracted: reason for ED, study type (interventional [In] vs observational), sponsor (yes vs not). ED rate was compared between CT discontinued for C19P or not (χ2);p < 0.05 was set as statistically significant. A multiple linear regression analysis was also conducted to identify independent factors of ED. Results: 9990 CT were identified and 7901 CT were excluded because not related to prostate cancer. Thus, 559 CT were included: 67% was T, 27% was W and 5% was S. Among CT classified as T, W and S, the frequency of In CT were 90%, 82% and 81% respectively, while the frequency of sponsored CT was 48%, 27% and 19% respectively. The most common reasons for ED were: “poor accrual” (31%), “lack of funding” (7%) and “sponsor decision” (5%). No reason for ED was available for 13% of CT. Ten (2%) CT were discontinued for C19P (20% was T, 10% was W and 70% was S). Comparing CT discontinued due to C19P with those discontinued due to other causes, a lower rate of In-CT (88% vs 91%, p<0.05) was found in the C19P group. At the multiple linear regression analysis, it was found that C-19 was strongly positively correlated with ED (coefficient 0,62677, p<0.0001) whereas sponsored CT resulted negatively correlated with ED (coefficient -0,03717, p=0.0369). Conclusions: “Poor accrual” continues to be the main reason for ED of cancer CT, whereas C19P represents a new additional cause of ED. Sponsored trials showed less risk for ED. Further research is needed to maximize the expected benefit of cancer CT, reducing the anticipated risks.

Serological Response to COVID-19 Vaccination in Patients with Cancer older than 80 years

Background: The randomized study of BNT162b2 mRNA vaccine enrolled 43,548 patients (pts) aged between 16 and 91 years, but excluded pts receiving immunosuppressive therapy and those diagnosed with an immunosuppressive condition. Considering the important need of real-life data related to COVID-19 vaccine in older pts with cancer, we decided to conduct a study to evaluate the seroprevalence of the SARS-CoV-2 IgG in cancer patients aged ≥ 80 years one month after administering the second dose of BNT162b2 vaccine. Materials and Methods: This was a spontaneous, notsponsored, mono-institutional, cross-sectional control study conducted at San Camillo-Forlanini Hospital in Rome. We screened 74 older patients with cancer, 45 of them accepted to receive the vaccination and we collected serum samples from 36 pts. A group of medical doctors and nurses of our Hospital was used as a control in a 1:2 ratio. Results: Pts' data are summarized in Table 1. Median serum IgG were 2396,10 AU/ml (range 0-32763,00) in cancer pts and 8737,49 AU/ml (398,90-976280,00) in control group, p<0.0001. Additional subgroup analyses were performed comparing males and females, chemotherapy versus other therapies (immunotherapy, targeted therapy), solid tumors versus hematological malignancies, early (I-II) versus advanced (III-IV) stage of disease, continuative corticosteroid use or not. None of them reached statistical significance. None of the pts enrolled in this study experienced COVID-19 infection after vaccination, regardless of the level of IgG response. Conclusions: Our study shows for the first time that cancer pts cancer aged =80 years can have a serological response to the BNT162b2 COVID-19 vaccine one month after vaccination. Additional serological tests will be performed after 6 and 12 months from vaccination in order to evaluate the duration of immunological response in our pts.

Why do cancer clinical trials (CT) discontinue prematurely in the era of COVID-19?

Background: The COVID-19 pandemic (C19P) is causing several detrimental effects on cancer care globally. CT are crucial to obtain high quality literature evidence and “poor accrual” is the most common reason for their early discontinuation (ED). At our best knowledge, no data are available on ED of cancer CT after the beginning of C19P. Methods: ClinicalTrial.gov was queried for terminated (T), withdrawn (W) and suspended (S) CT for the following terms: “cancer”, “neoplasm”, and “tumor”. The search was made for all the CT available from the inception to 26th February 2021, without any restrictions. The following characteristics were extracted: reason for ED, study type (interventional [In] vs observational), sponsored (yes vs not). ED rate was compared between CT discontinued for C19P or not (χ2);p<0.05 was set as statistically significant. A multiple linear regression analysis was also conducted to identify independent factors of ED. Results: 9990 CT were identified, but 765 CT were excluded as not related to cancer. Thus, 9225 CT were included (66% was T, 23% was W and 4% was S). Among CT classified as T, W and S, the frequency of In CT was 92%, 88% and 85% respectively, while the frequency of sponsored CT was 46%, 35% and 26% respectively. The most common reasons for ED were: “poor accrual” (29%), “lack of funding” (6%) and “sponsor decision” (5%). No reason for ED was available for 15% of CT. One hundred (1%) CT were discontinued due to C19P (27% was T, 7% was W and 66% was S). Comparing CT discontinued due to C19P with those discontinued due to other reasons, a lower rate of In-CT (73% vs 91%, p<0.05) and sponsored CT (14% vs 42%, p<0.05) was found in the C19P group. At the multiple linear regression analysis, C19P was strongly positively correlated with ED (coefficient 0.59952, p<0.0001) whereas sponsored CT resulted as negatively correlated with ED (coefficient -0.02746, p<0.0001). Conclusions: “Poor accrual” continues to be the main reason for ED of cancer CT, but C19P represents a new additional cause of ED. Sponsored trials showed less risk for ED. Further research is needed to maximize the expected benefit of cancer CT, reducing the anticipated risks. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Minoca or post-infection coronary vasculitis of SARS-CoV2?

SARS-COV2 causes a large inflammatory response. The effects on the cardiac and vascular system are still being studied. Clinical Case: A 50-year-old man came to the emergency room of our hospital for fever and asthenia. For the positivity for SARS-COV2 and radiographic finding of bilateral interstitial pneumonia, he was hospitalized at the U.O. COVID, where for hypoxemic respiratory insufficiency he was subjected to ventilotherapy with CPAP. The improvement in respiratory failure and the negativization of the nasopharyngeal swab for SARS-COV2 indicated discharge. The patient underwent a pre-discharge ECG which showed negative T waves in the inferior site and from V3-V6 not present in the previous one. Dosage of cardiac cytonecrosis indices showed troponin T HS (34, ng/l v.n. <14 ng/l) slightly increased;blood chemistry tests show CRP equal to 26 mg/dl and normal leukocyte number and formula. The 2d color Doppler echocardiogram reported: “Akinesia of the mid-apical portion of the septum, apex and lower wall, with an FE equal to 45%. Presence of a slight pericardial detachment of the lateral wall of the left ventricle.” The patient was transferred to our U.O. of Cardiology, who underwent coronary angiography showing normal coronaries. With the suspicion of SARS-COV2 myocarditis, the patient underwent cardiac MRI which confirmed the akinesias shown on the echocardiogram. Late enhancement in subendocardial disposition consistent with an acute ischemic injury in these sites was evident on T2- weighted sequences. Discussion: Normal coronary myocardial infarctions (MINOCA) are described in the literature and it is hypothesized that the inflammatory reaction and hypoxia caused by SARS-COV2 may play a central role in the pathogenesis of ischemic disorder. The district nature of the lesion compatible with a coronary atherosclerotic obstruction not detected on angiographic examination, however, needs to be clarified. The vasculitis resulting from the infection can explain the locality of the lesion on the echocardiogram and on the ECG but opens the discussion on therapeutic choices.

Septic shock and reversible right ventricle dysfunction

Background: Right ventricle involvement during sepsis is often misunderstood, although it is described that an altered performance of the right ventricle is present in 2/3 of cases of moderate to severe forms of sepsis. Clinical Case: 30 years old woman without known cardiovascular risk factors with a history of multiple psychiatric disorders. Access to the emergency departement of our hospital complaining asthenia and hypotension. The patient underwent cardiological evaluation with EKG findings of sinus tachycardia and diffuse ST-T anomalies and bidimensional echocardiogram negative for biventricular kinetic anomalies. Laboratory evidence of creatinine 2.07 mg/dl, slight increase in inflammation indices (CRP 38 mg/dl) and anemia (HB: 9.2 g/l). Swab for SARS-COV2 was negative. The patient was then admitted to the local department of Medicine. During hospitalization, evidence of hypotension and progressive worsening of inflammation indices. Due to addominal pain, the patient underwent EGDS showing hiatal hernia. Subsequent onset of fever, with negative urine culture and positive blood cultures for S. Epidermidis. In addition, due to the detection of involuntary movements of the limbs and eyelids she was subjected to cerebral MRI in suspicion of encephalitis, that was excluded. At a subsequent cardiological and echocardiographic evaluation, finding of “Hypocontractile right ventricle, volume overload of the right sections with paradoxical movement of the interventricular septum, PAPs: 50 mmHg”. On chestabdomen CT scan “absence of focal pulmonary lesions and bilateral pleural effusions, patent pulmonary circulation, absence of thrombotic filling defects”. The patient was therefore transferred to our cardiology departement with diagnosis of septic shock. During hospitalization, evidence of hypokalemia, long QT interval (> 500 msec) and self-limiting polymorphic ventricular tachycardia. After long-term therapy with inotropics and antibiotics, we found a significant clinical improvement with echocardiographic evidence of complete recovery of right ventricular performance. The case described is a paradigmatic example of reversible alteration of right ventricle systolic function during septic shock (severe sepsis). The different pathogenetic determinants, however, are still debated. There are two possible hypotheses: inflammatory myocardial right ventricle involvement (myocarditis) or vasculitic involvement of right ventricle, sustained by inflammatory stress and bacteremia.