SARS-CoV-2 convalescent plasma therapy in pediatric patient after hematopoietic stem cell transplantation.

Immunocompromised patients, including HSCT recipients, may have a poor prognosis after contracting COVID-19 due to the absence of a pathogen-specific adaptive immune response. One of the possible options for severe COVID-19 treatment may be the transfusion of hyperimmune SARS-CoV-2 convalescent plasma. A 9-month-old girl with juvenile myelomonocytic leukemia received an HSCT from a haploidentical donor. On day +99, during routine virologic monitoring, SARS-CoV-2 was detected without any clinical symptoms. On day +144, the child developed a polysegmental bilateral viral pneumonia with 60 % damage to the lung tissue and confirm a positive SARS-Cov-2 results in throat swab. The patient was treated with tocilizumab and three doses of fresh frozen plasma obtained from a SARS-CoV-2 convalescent patient. Therapy with tocilizumab and three doses of fresh frozen plasma was well tolerated. In spite of full resolution of the lung lesions, complete elimination of SARS-CoV-2 has not been achieved 4 months after the first detection, which is due to persistence of secondary immunodeficiency after HSCT and the lack of reconstitution of the adaptive immune response. This case represents a demonstration of an atypical course of COVID-19 and the delayed development of lung lesions, which was most likely associated with the features of the patient's immune status after HSCT. SARS-CoV-2 convalescent plasma in combination with other therapeutic approaches is one of the possible curative options for this clinical situation.

Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαß and CD19 Depletion in Children with Primary Immunodeficiency Syndromes.

The transplantation of stem cells from a matched unrelated donor (MUD) or a haploidentical mismatched related donor (MMRD) is a widely used variant of curative treatment for patients with primary immunodeficiency (PID). Currently, different strategies are used to reduce the risk of post-transplant complications and enhance immune reconstitution. We report the preliminary results of MUD and MMRD transplantation with TCRαß/CD19 depletion in patients with PID (trial registered at www.clinicaltrials.gov as NCT02327351). Thirty-seven PID patients (median age, 2.6 years; range, .2 to 17) were transplanted from MUDs (n = 27) or haploidentical MMRDs (n = 10) after TCRαß(+)/CD19(+) graft depletion. The median numbers of CD34(+) and TCRαß(+) cells in the graft were 11.7 × 10(6)/kg and 10.6 × 10(3)/kg, respectively. Acute graft-versus-host disease (GVHD) was observed in 8 patients (22%), without a statistically significant difference between MUDs and MMRDs; 7 of these patients had grade II acute GVHD and responded to first-line therapy, whereas 1 patient had grade IV acute GVHD with transformation to extensive chronic GVHD. Primary and secondary graft failure (nonengraftment or rejection) was observed in 10 patients (27%), 9 of whom were treated with 1 alkylating agent in the conditioning regimen. All these patients were successfully retransplanted with different rescue protocols. Preliminary data on immune reconstitution were very encouraging. Most patients had significant numbers of T lymphocytes detected on the first assessment (day +30) and more than 500 T cells/µL, on day +120. Based on our preliminary data, no significant difference was seen between MMRD and MUD hematopoietic stem cell transplantation (HSCT). With a median follow-up period of 15 months, the cumulative probabilities of overall patient survival and transplant-related mortality were 96.7% and 3.3%, respectively. Based on the results, the ability to control the main post-transplant complications and the immune reconstitution rates are the main factors leading to successful outcome in patients with PID after TCRαß(+)-depleted HSCT.

Pathway-based personalized analysis of breast cancer expression data.

INTRODUCTION: Most analyses of high throughput cancer data represent tumors by "atomistic" single-gene properties. Pathifier, a recently introduced method, characterizes a tumor in terms of "coarse grained" pathway-based variables. METHODS: We applied Pathifier to study a very large dataset of 2000 breast cancer samples and 144 normal tissues. Pathifier uses known gene assignments to pathways and biological processes to calculate for each pathway and tumor a Pathway Deregulation Score (PDS). Individual samples are represented in terms of their PDSs calculated for several hundred pathways, and the samples of the data set are analyzed and stratified on the basis of their profiles over these "coarse grained", biologically meaningful variables. RESULTS: We identified nine tumor subtypes; a new subclass (comprising about 7% of the samples) exhibits high deregulation in 38 PKA pathways, induced by overexpression of the gene PRKACB. Another interesting finding is that basal tumors break into two subclasses, with low and high deregulation of a cluster of immune system pathways. High deregulation corresponds to higher concentrations of Tumor Infiltrating Lymphocytes, and the patients of this basal subtype have better prognosis. The analysis used 1000 "discovery set" tumors; our results were highly reproducible on 1000 independent "validation" samples. CONCLUSIONS: The coarse-grained variables that represent pathway deregulation provide a basis for relevant, novel and robust findings for breast cancer. Our analysis indicates that in breast cancer reliable prognostic signatures are most likely to be obtained by treating separately different subgroups of the patients.

Role of Non-Steroidal Anti-Inflammatory Drugs in Gynecology.

This review summarizes the current use of non-steroidal anti-inflammatory drugs (NSAIDs) in obstetrics, gynecology and infertility. These medications are commonly used in different fields of reproductive medicine, for pain management after operative procedures and to relieve dysmenorrhea. In addition to their analgesic effect, NSAIDs are helpful in the management of menorrhagia by decreasing menstrual blood loss. NSAIDs alleviate pain associated with medical abortion, assist in undertaking natural cycle in-vitro fertilization by preventing follicular rupture and reducing premature ovulation, and serve as tocolytics in preterm labor. New NSAIDs may have a growing role in management of women's health.

Fertility issues in women with diabetes.

Diabetes mellitus Type 1 and Type 2 should be considered in the differential diagnosis of menstrual abnormalities and infertility. The reproductive period of diabetic women may be reduced due to delayed menarche and premature menopause. During the reproductive years, diabetes has been associated with menstrual abnormalities, such as oligomenorrhea and secondary amenorrhea. It was found that better glycemic control and prevention of diabetic complications improves these irregularities and increases fertility rates close to those that are seen in the general population. Women with persistent menstrual abnormalities despite adequate treatment need to be approached by broader evaluation, which will include the examination of the hypothalamic-pituitary-ovarian axis and the hormonal status, presence of autoimmune thyroid disease and antiovarian autoantibodies, and hyperandrogenism.

Ibuprofen and paracetamol for pain relief during medical abortion: a double-blind randomized controlled study.

OBJECTIVE: To determine the efficacy of a nonsteroidal anti-inflammatory drug vs. paracetamol in pain relief during medical abortion and to evaluate whether nonsteroidal anti-inflammatory drugs interfere with the action of misoprostol. DESIGN: A prospective double-blind controlled study. SETTING: University-affiliated tertiary hospital. PATIENT(S): One hundred twenty women who underwent first-trimester termination of pregnancy. INTERVENTION(S): Patients received 600 mg mifepristone orally, followed by 400 microg of oral misoprostol 2 days later. They were randomized to receive ibuprofen or paracetamol when pain relief was necessary. Patients completed a questionnaire about side effects and pain score and returned for an ultrasound follow-up examination 10-14 days after medical abortion. MAIN OUTCOME MEASURE(S): Success rates, as defined by no surgical intervention, and pain scores were assessed. RESULT(S): Ibuprofen was found to be statistically significantly more effective for pain relief after medical abortion compared with paracetamol. There was no difference in the failure rate of medical abortion, and the frequency of surgical intervention was slightly higher in the group that received paracetamol (16.3% vs. 8.5%). CONCLUSION(S): Ibuprofen was found to be more effective than paracetamol for pain reduction during medical abortion. A history of surgical or medical abortion was predictive for high pain scores. Despite its anti-prostaglandin effects, ibuprofen use did not interfere with the action of misoprostol.