No abstract

Idecabtagene vicleucel (ide-cel) was FDA approved in March 2021 for the treatment of relapsed/refractory multiple myeloma (RRMM) after 4 lines of therapy. On the KarMMa trial, grade ≥3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard of care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day 90 follow-up. Data was censored at day 100. Grade ≥3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell (pRBC) transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin (IVIG) to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 - 100 were 50% bacterial and 42% viral; only 13% were grade ≥3. On univariate analysis, high pre-CAR-T marrow myeloma burden (>/= 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥3 anemia at pre-LD were associated with grade ≥3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection.

This study tested the hypothesis that reciprocal communication occurs between macrophages and cultured human endometrial stromal cells and that this communication may contribute to the pathology of endometriosis. An endometrial stromal cell line (T-HESC) was treated with macrophage conditioned medium (CM) ± estradiol+progesterone. Macrophages were treated without or with T-HESC CM. DNA microarray identified 716 differentially expressed genes in T-HESC cells in response to factors secreted by macrophages. Up-regulated genes in T-HESC included IL8/CXCL8, MMP3, phospholamban, CYR61/CCN1, CTGF/CCN2, tenascin C, and NNMT, whereas integrin alpha 6 was down-regulated. In contrast, 15 named genes were differentially expressed in macrophages in response to factors secreted by endometrial stromal cells. The data document reciprocal communication between macrophages and endometrial stromal cells and suggest that interaction with macrophages stimulates the expression of genes in endometrial stromal cells that may support the establishment of endometriosis.

Immune system cells and cells of the endometrium have long been proposed to interact in both physiological and pathological processes. The current study was undertaken to examine communication between cultured monocytes and endometrial stromal cells and also to assess responses of endometrial stromal cells for treatment with estradiol (E) in the absence and presence of medroxyprogesterone acetate (P). A telomerase-immortalized human endometrial stromal cell (T-HESC) line and the U937 monocyte cell line were used. Telomerase-immortalized human endometrial stromal cells were treated with E +/- P +/- monocyte conditioned medium; U937 were treated +/- T-HESC conditioned medium. Gene expression in response to treatment was examined by DNA microarray. Bidirectional communication, as demonstrated by changes in gene expression, clearly occurred between U937 monocytes and T-HESC.

No abstract

Hypertension is sexually dimorphic and modified by removal of endogenous sex steroids. This study tested the hypothesis that endogenous gonadal hormones exert differential effects on protein expression in the kidney and mesentery of SHR. At ~5 weeks of age male and female SHR underwent sham operation, orchidectomy, or ovariectomy (OVX). At 20-23 weeks of age, mean arterial pressure (MAP) was measured in conscious rats. The mesenteric arterial tree and kidneys were collected, processed for Western blots, and probed for Cu Zn superoxide dismutase (SOD1), soluble epoxide hydrolase (sEH), and Alpha 2A adrenergic receptor (A2AR) expression. MAP was unaffected by ovariectomy (Sham 164 ± 4: Ovariecttomy 159 ± 3 mm Hg). MAP was reduced by orchidectomy (Sham 189 ± 5:Orchidectomy 167 ± 2 mm Hg). In mesenteric artery, SOD1 expression was greater in male versus female SHR. Orchidectomy increased while ovariectomy decreased SOD1 expression. The kidney exhibited a different pattern of response. SOD1 expression was reduced in male compared to female SHR but gonadectomy had no effect. sEH expression was not significantly different among the groups in mesenteric artery. In kidney, sEH expression was greater in males compared to females. Ovariectomy but not orchidectomy increased sEH expression. A2AR expression was greater in female than male SHR in mesentery artery and kidney. Gonadectomy had no effect in either tissue. We conclude that sexually dimorphic hypertension is associated with regionally specific changes in expression of three key proteins involved in blood pressure control. These data suggest that broad spectrum inhibition or stimulation of these systems may not be the best approach for hypertension treatment. Instead regionally targeted manipulation of these systems should be investigated.

Background Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) that is a part of the normal human skin flora. Even though it belongs to CoNS family, it can cause severe and destructive infections in a similar fashion to Staphylococcus aureus . Skin and soft tissue infections (SSTI), bacteremia and endocarditis are amongst the most common clinical presentations. Diagnosis and clinical presentation of infections caused by S. lugdunensis in cancer patients is limited. Materials and Methods We performed a retrospective chart review of 24 patients who had cultures positive for S. lugdunensis . Out of 24 patients, 14 patients were diagnosed with a true infection and 10 other patients were considered to be colonized with this pathogen. We analyzed clinical manifestation, treatment and response to therapy. Results SSTI was the most common presentation in our study patients. All patients diagnosed with SSTI had a prior surgery or an invasive procedure at the affected site. Five urinary tract infections (UTIs), one catheter-associated bloodstream infection, and a deep pelvic abscess were other reported infections in our study. We observed that S. lugdunensis remains susceptible to a variety of antibiotics, with all isolates susceptible to vancomycin and linezolid and most remain susceptible to fluoroquinolone and trimethoprim/ sulfamethoxazole. All 14 patients received antibiotics and improved. Conclusion In our case series, SSTI was common and diagnosed in 50% of the patients with clinically significant isolates for S. lugdunensis . This is consistent with prior studies indicating that S. lugdunensis is a significant pathogen in SSTIs. UTI was the second most common infection type in our patient population.

Objective The aim of this study was to identify causative organisms of acute rhinosinusitis in immunosuppressed patients by a retrospective chart review. Methods Records were reviewed using International Classification of Disease, Ninth Edition codes for inpatient treatment of acute sinusitis. Patients were included only if they had formal sinus cultures obtained and were immunosuppressed, either carrying a diagnosis of a hematologic malignancy or receiving chemotherapy. Demographics, underlying malignancy, and culture results were recorded. Results Records of 74 patients with 104 cultures were obtained. There were 43 males and 31 females. The mean age was 51. The most common primary diagnoses were leukemia (65%) and lymphoma (23%). Sixty cultures resulted in either no growth or growth of usual respiratory flora. Of the 44 positive cultures, 5 were polymicrobial, resulting in 61 organisms isolated in total. Bacteria cultured were 73% Gram positive, whereas 27% were Gram negative. The most common Gram-positive organisms cultured were Staphylococcus species. Pseudomonas species were the predominant Gram-negative bacteria. Thirteen samples grew fungal organisms. Conclusions Medical management of sinusitis in an immunosuppressed patient seems to be adequate in most cases. Patients who fail to improve should undergo evaluation by an otolaryngologist to obtain cultures for directed antibiotic therapy. Infections by Staphylococcus species as well as quinolone- and cephalosporin-resistant Gram-negative organisms may be encountered, and clinicians should suspect their presence in patients with persistent disease and expand their antibiotic coverage appropriately.