Reply to “successful early use of anti-SARS-CoV-2 monoclonal neutralizing antibodies in SARS-CoV-2 infected hematological patients—A Czech multicenter experience”: A case series of SARS-CoV-2 Omicron infection and aggressive lymphoma in the Sotrovimab era

A prospective multicentre experience of early administration of anti-SARS-CoV-2 spike protein neutralizing monoclonal antibodies (MA) with efficacy among patients with hematological malignancies and early-stage COVID- 19 was reported by Weinbergerová et al. The study validated the safety and efficacy of MA early use among hematological patients with newly diagnosed early-stage COVID-19 in terms of alleviating infection course and decreasing mortality. However no reference to new variant (Delta and Omicron) or other MA (e.g., Sotrovimab) has been reported. We reported our monocentric experience of 8 aggressive lymphoma patients with Omicron infection, 7 of whom treated with this MA in our Institution between December 2021 and February 2022. Among the patients treated with Sotrovimab nobody experienced neither SARS-CoV2 reactivation, nor other infectious events. One patients on active lymphoma treatment was hospitalized for pneumonia and treated with remdesivir. In 4/8 patients negativization of molecular swab occurred concomitantly to symptoms resolution with a median of 5.25 days, while the other 4 patients remained persistently positive with a median of 26.3 days. In this group, in order to maintain the chemo/chemoimmunotherapy (CT/CIT) dose-density, lymphoma treatment was reassumed independently on molecular swab analysis. SARS-CoV-2 negativization occurred with a median of 7.7 days after the resumption of CT/CIT. The one patient treated with remdesivir, although still positive to molecular swab, restarted R-COMP regimen at symptoms resolution too, but experienced an Omicron pneumonia exacerbation. This is the first case series reported in literature of patients affected by Omicron variant in which Sotrovimab seems to provide a resolution of COVID-19 disease, even in patient with molecular swab positive persistence too. Patients with aggressive lymphoma histologies should not be deprived of the best available treatment of their disease after sotrovimab administration, even in the presence of a still positive Omicron swab.     

Multistage drug effects of ketamine in the treatment of major depression

A substantial number of patients diagnosed with major depression disorder show poor or no response to standard antidepressive drugs. Recent studies showed that ketamine promotes a rapid and sustained antidepressive effect in treatment-resistant depression. Importantly, after a single dose, such antidepressant action appears very fast, reaching maximum efficacy after 1–2 days before it slowly decays after 3–7 days. This temporal pattern is especially interesting since most effects are investigated following single, subanesthetic doses. This means that effects are observed at time points when the blood levels have long fallen below any active threshold. Mechanisms of action thus may be sought either in secondary or compensatory processes, which develop after acute systemic derangement or in molecular downstream mechanisms of action, which after initiation do not require the presence of active drug levels. We here review acute and delayed effects of subanesthetic ketamine infusion and discuss potential origins of antidepressant drug action. We will provide evidences that both acute effects on abnormal network configuration and delayed effects at the level of homeostatic synaptic plasticity may be necessary for antidepressant action. We further argue that such effects should be followed by a temporally well-defined exploitation of these transient changes by therapeutic processes, aiming at sustained changes of network configuration via psychotherapeutic or other methods.

     

Reggio Emilia,Vygotsky, and Family Childcare: Four American Providers Describe their Pedagogical Practice

This case study considers pedagogical techniques used in family childcare to promote children's learning experiences. Data extracted from an earlier study were used to inform this examination of four family childcare providers’ pedagogy. In the current study, I use socio-cultural theory and the Reggio Emilia approach to address the following research question: how do family childcare providers describe learning experiences of children in their care? Four themes emerged from the data: responsiveness to children, children's play, reflective thinking, and didactic teaching. The study indicated that providers’ work is informal, but nonetheless these caregivers follow a natural, experiential learning, along with more didactic practices common to traditional classrooms.     

“You Live Where?!” Lesbian Mothers' Attachment to Nonmetropolitan Communities

A positive attachment to one's residential community has been linked to better mental health ( McLaren, 2009 ), stronger social support ( Young, Russell, & Powers, 2004 ), and a higher quality of life ( Mak, Cheung, & Law, 2009 ). Attachment to residential community has been understudied in research on lesbian, gay, bisexual, and transgender (LGBT) families. The current study attempts to fill this gap by using family and minority stress theories to examine the predictors of residential community attachment among 77 lesbian mothers living in nonmetropolitan communities. Our findings indicate that stronger residential community attachment is predicted by more frequent contact with family of origin, low religiosity, and an interaction between close LGBT friendships and the presence of at least one local LGBT organization. Contrary to expectations, anti‐LGBT victimization perpetrated by community members did not have an effect on residential community attachment.     

The population of paroxysmal nocturnal hemoglobinuria neutrophils deficient in decay-accelerating factor is also deficient in alkaline phosphatase

In patients with paroxysmal nocturnal hemoglobinuria (PNH) the RBCs, neutrophils (PMNs), monocytes, and platelets derived from the abnormal clone are deficient in the complement-regulatory protein decay-accelerating factor (DAF). RBC acetylcholinesterase (AChE) and leukocyte alkaline phosphatase (LAP) activities are also characteristically low. DAF, AChE, and LAP are known to be anchored within cell membranes to glycophospholipid-containing phosphatidylinositol (PI). Because PNH progenitors contain DAF that appears to be lost with maturation, it has been proposed that this disorder results from abnormal tethering of these and possibly other proteins to membrane PI. We were puzzled, therefore, that our two PNH patients consistently had normal LAP levels. Consequently, we studied their isolated PMNs to compare DAF and LAP activities in individual cells. PMNs were separated by flow cytometry into DAF-positive and -negative populations by using rabbit anti-DAF antiserum and fluorescein-conjugated goat antirabbit IgG. In both patients the majority of PMNs were DAF deficient, and these cells contained very little alkaline phosphatase activity. In contrast, the smaller, DAF-positive cell populations were phosphatase replete. This is the first demonstration that abnormalities in DAF and LAP activity occur in the same PNH PMN population and strengthens the hypothesis that defective anchoring of proteins to membrane glycophospholipid underlies the pathophysiology of this disorder.     

Different methods of creatinine measurement significantly affect MELD scores.

Bilirubin (Bil) interferes with creatinine (Cr) measurement. Different laboratory methods are used to overcome this problem. Model for end-stage liver disease (MELD) scoring incorporates Cr and is used to prioritize patients for liver transplantation. Thus, MELD scores may vary with different Cr measurements influencing patients' priority. Our aim was to evaluate 4 different Cr assays (O'Leary modified Jaffe [mJCr], compensated [rate blanked] kinetic Jaffe [cJCr], enzymatic [ECr], and standard kinetic Jaffe [JCr]) in patients with abnormal liver function tests and assess changes in MELD score. A total of 403 consecutive samples from 158 patients' Cr assays were evaluated.. Bland-Altman plots and MELD scores were also evaluated for each assay. Agreement was found to be poor among all Cr assays. Increased variability in Cr occurred with increasing Bil concentrations: Bil <100 micromol/L or=400micromol/L or=3-point difference in 78%. When MELD was >or=25 (mJCr as reference; mean, 30.5 points), MELD variation was greatest: mean, 28 (MELD cJCr), 27.5 (MELD ECr), and 28.4 (MELD JCr) (P < 0.001). In conclusion, there is poor agreement among different assays for Cr. As Bil concentration rises, there is greater variability in each creatinine measurements and thus greater variability in MELD scores that, this affect prioritization for liver transplantation.