Paradoxical effect of SARS-CoV-2 infection in patients with immune thrombocytopenia.

Thrombocytopenia has been identified as a common complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the general population. In an attempt to determine the impact of coronavirus disease 2019 (COVID-19) in patients with immune thrombocytopenia (ITP), a retrospective single-centre study was performed. Thrombocytosis was observed in patients with chronic ITP after SARS-CoV-2 infection, frequently needing treatment adjustment or even discontinuation of therapy. Relapses and newly diagnosed cases showed a fast response after initial treatment compared to ITP. Reduced immune activity due to lymphopenia during COVID-19 could explain this paradoxical effect, although further studies are needed.

Managing the front-line treatment for diffuse large B cell lymphoma and high-grade B cell lymphoma during the COVID-19 outbreak.

The COVID-19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment who represent a vulnerable population for SARS-CoV-2 infection. Aggressive lymphoid neoplasms, such as diffuse large B cell lymphoma and high-grade B cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed to minimise the risk of SARS-CoV-2 infection while continuing haematological treatment. In this report, we analyse the management of front-line therapy in 18 patients during the COVID-19 outbreak, as well as the results of the implemented measures in their outcome.

Effects of different fluences of low-level laser therapy in an experimental model of spinal cord injury in rats.

The aim of this study was to evaluate the in vivo response of different fluences of low-level laser therapy (LLLT) on the area of the injury, inflammatory markers, and functional recovery using an experimental model of traumatic spinal cord injury (SCI). Thirty two rats were randomly divided into four experimental groups: control group (CG), laser-treated group 500 J/cm2 (L-500), laser-treated group 750 J/cm2 (L-750), and laser-treated group 1000 J/cm2 (L-1000). SCI was performed by an impactor equipment (between the ninth and tenth thoracic vertebrae), with a pressure of 150 kdyn. Afterwards, the injured region was irradiated daily for seven consecutive sessions, using an 808-nm laser, at the respective fluence of each experimental groups. Motor function and tactile sensitivity were performed on days 1 and 7 post-surgery. Animals were euthanized on the eighth day after injury, and the samples were retrieved for histological and immunohistochemistry analyses. Functional evaluation and tactile sensitivity were improved after LLLT, at the higher fluence. Additionally, LLLT, at 750 and 1000 J/cm2, reduces the lesion volume and modulates the inflammatory process with decrease of CD-68 protein expression. These results suggest that LLLT at higher doses was effective in promoting functional recovery and modulating inflammatory process in the spinal cord of rats after SCI.

Clonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma.

Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses is one of the biggest clinical challenges. TP53 alterations are established high-risk markers and are included in the current disease staging criteria. KRAS is the most frequently mutated gene affecting around 20% of MM patients. Applying Clonal Competition Assays (CCA) by co-culturing color-labeled genetically modified cell models, we recently showed that mono- and biallelic alterations in TP53 transmit a fitness advantage to the cells. Here, we report a similar dynamic for two mutations in KRAS (G12A and A146T), providing a biological rationale for the high frequency of KRAS and TP53 alterations at MM relapse. Resistance mutations, on the other hand, did not endow MM cells with a general fitness advantage but rather presented a disadvantage compared to the wild-type. CUL4B KO and IKZF1 A152T transmit resistance against immunomodulatory agents, PSMB5 A20T to proteasome inhibition. However, MM cells harboring such lesions only outcompete the culture in the presence of the respective drug. To better prevent the selection of clones with the potential of inducing relapse, these results argue in favor of treatment-free breaks or a switch of the drug class given as maintenance therapy. In summary, the fitness benefit of TP53 and KRAS mutations was not treatment-related, unlike patient-derived drug resistance alterations that may only induce an advantage under treatment. CCAs are suitable models for the study of clonal evolution and competitive (dis)advantages conveyed by a specific genetic lesion of interest, and their dependence on external factors such as the treatment.

Case Report: COVID-19 with Bilateral Adrenal Hemorrhage.

A 70-year-old Dominican Republic man presented with lower back pain for 10 days. Fifteen days before pain onset, he had low-grade fever, chills, and asthenia, and 4 days before admission, he had constipation, malaise, generalized weakness, anorexia, nausea, and vomiting. On admission, the patient was afebrile and hypotensive, with a heart rate of 105 and an oxyhemoglobin saturation on room air of 95%. Hyponatremia, lymphopenia, elevated C-reactive protein, and ferritin were observed in complementary tests. Computed tomography (CT) scan showed findings consistent with COVID-19 bilateral bronchopneumonia, and an increase in size and blurring (loss of the Y shape) of both adrenals indicative of acute bilateral adrenal hemorrhage. The patient tested negative by reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal swab, yet positive for IgG and IgM by ELISA, suggesting COVID-19 diagnosis.