Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases.

BACKGROUND: The indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation. METHODS: We conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome. RESULTS: Forty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29-37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1-4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5-14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15-1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15-4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5-100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0-100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births. CONCLUSIONS: Oocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.

Prevention of acute graft-versus-host disease in adult T-cell leukemia-lymphoma patients who received mogamulizumab before allogeneic hematopoietic cell transplantation.

Mogamulizumab (Mog) is effective against adult T-cell leukemia-lymphoma (ATL), but as we reported previously, Mog increases the incidence of severe acute GVHD when administered before allogeneic hematopoietic cell transplantation (allo-HCT). Here, we report the cases of two ATL patients who did not develop acute GVHD despite receiving Mog before allo-HCT. Case 1: a 63-year-old female who underwent allo-HCT from an HLA-matched donor 2 months after the last dose of Mog. Case 2: a 47-year-old male with ATL that relapsed 3 months after first allo-HCT. He received eight doses of Mog and underwent a second allo-HCT from a haploidentical donor 4 months after the last dose of Mog. Mog blood levels were measured and lymphocytes analyzed by mass cytometry. Mog blood levels measured before starting the conditioning regimens were low. A small proportion of regulatory T cells (Tregs) was detected before and shortly after allo-HCT. When using Mog before allo-HCT, it is important to consider the number of Mog doses and the interval from the last dose of Mog to allo-HCT. Analyzing Mog blood levels and Treg counts before and after allo-HCT should also be useful.

Neuroprotective effects of aromatic turmerone on activity deprivation-induced apoptosis in cerebellar granule neurons.

Ar-turmerone, which is a major bioactive component found in the essential oil derived from Curcuma longa, has been reported to inhibit proliferation and induce apoptosis in cancer cell lines. Recently, ar-turmerone has been reported to increase the proliferation of neuronal stem cells, in contrast to its actions in cancer cells. These observations raise the possibility that ar-turmerone serves specific functions in neuronal cell lineages. However, the effects of ar-turmerone on postmitotic neurons remain elusive. In the present study, we investigated the neuroprotective functions of ar-turmerone in primary cerebellar granule neuronal cultures. We found that ar-turmerone increased the survival of neurons following activity deprivation. Consistently, the induction of cleaved caspase-3, a hallmark of apoptosis, was prevented by ar-turmerone, although neither the level of reactive oxygen species nor the mitochondrial membrane potential was affected. This study reports a neuroprotective function for ar-turmerone, providing new insights into the potential therapeutic applications of ar-turmerone for neurological disorders.

Outcome of primary vitrectomy in phakic patients aged younger than 50 years with rhegmatogenous retinal detachments.

PURPOSE: To evaluate the visual outcome, primary anatomic success, and cataract progression of phakic eyes of patients aged younger than 50 years treated for rhegmatogenous retinal detachment (RRD) with primary pars plana vitrectomy (PPV). METHODS: This was a retrospective, observational, cross-sectional study. The data from 53 RRD patients undergoing PPV were analyzed. The time course changes in best-corrected visual acuity (BCVA) and cataract formation were examined. RESULTS: The 53 patients had a mean age of 37.8 years. Forty-eight eyes (90.6 %) achieved anatomic success after the primary surgery. The BCVA improved significantly after surgery (mean ± SD -0.091 ± 0.146) when compared with the baseline (mean ± SD 0.214 ± 0.597; P = 0.0001). No patient aged younger than 40 years (mean 32.5 years; range 17-39) developed significant lens opacity or received cataract surgery within the first 3 years. Of the patients aged older than 40 years (mean 43.8 years; range 40-49), 22 % developed significant lens opacity and received cataract surgery within the first 3 years. A significant difference was found in cataract progression between the two groups within the first 3 years (P = 0.0217), but not over the entire follow-up period (P = 0.1679). CONCLUSIONS: We found that lens-sparing PPV for RRD in patients aged younger than 50 years had a reasonable success rate, although cataract progression was evident during the follow-up period in patients aged older than 40 years.

A comparison of patient pain and visual outcome using topical anesthesia versus regional anesthesia during cataract surgery.

PURPOSE: The purpose of this study was to compare the level of patient pain during the phacoemulsification and implantation of foldable intraocular lenses while under topical, intracameral, or sub-Tenon lidocaine. PATIENTS AND METHODS: This was a retrospective study. Three hundred and one eyes subjected to cataract surgery were included in this study. All eyes underwent phacoemulsification surgery and intraocular lens implantation using topical, sub-Tenon, or intracameral anesthesia. The topical group received 4% lidocaine drops, and the intracameral group received a 0.1-0.2 cc infusion of 1% preservative-free lidocaine into the anterior chamber through the side port combined with topical drops of lidocaine. The sub-Tenon group received 2% lidocaine. Best-corrected visual acuity, corneal endothelial cell loss, and intraoperative pain level were evaluated. Pain level was assessed on a visual analog scale (range 0-2). RESULTS: There were no significant differences in visual outcome and corneal endothelial cell loss between the three groups. The mean pain score in the sub-Tenon group was significantly lower than that in the topical and intracameral groups (P=0.0009 and P=0.0055, respectively). In 250 eyes without high myopia (< -6D), there were no significant differences in mean pain score between the sub-Tenon and intracameral groups (P=0.1417). No additional anesthesia was required in all groups. CONCLUSION: Intracameral lidocaine provides sufficient pain suppressive effects in eyes without high myopia, while sub-Tenon anesthesia is better for cataract surgery in eyes with high myopia.

Elevated expression of coactivator-associated arginine methyltransferase 1 is associated with early hepatocarcinogenesis.

Aberrant expression of regulators for epigenetics is involved in tumorigenesis. There is an urgent need to identify and characterize regulators concerned with epigenetics in the early stages of hepatocarcinogenesis. In the present study, we found that the expression of coactivator-associated arginine methyltransferase 1 (CARM1), a histone methyltransferase that functions as a cofactor for nuclear hormone receptors and several transcription factors, was elevated in adenomas and aberrant in carcinomas during hepatocellular carcinogenesis. In addition to RNA expression, immunohistochemical staining of liver sections revealed that CARM1 was highly expressed in the nucleus of tumor marker glutathione S-transferase placental form (GST-P)-positive foci. Neoplastic transformation of GST-P-positive foci guides the formation of hepatocellular carcinomas. CARM1 expression was not elevated in GST-P-negative regions. Furthermore, a luciferase reporter analysis revealed that CARM1 activated the Gst-p promoter in H4IIE, a hepatocellular carcinoma cell line. This activation was mediated by the enhancer element responsible for the carcinogenic-specific expression of Gst-p and nuclear factor E2-related factor 2. Knockdown of Carm1 by shRNA in H4IIE cells inhibited cell proliferation. These findings suggest that aberrantly expressed CARM1 in tumor marker-positive cells promotes tumorigenesis in the early stages of hepatocarcinogenesis.

Efficacy of inverted internal limiting membrane flap technique for the treatment of macular hole in high myopia.

PURPOSE: To determine the effect of pars plana vitrectomy (PPV) with inverted internal limiting membrane (ILM) flap technique for macular hole with or without retinal detachment in highly myopic eyes. DESIGN: Retrospective, interventional case series. METHODS: Ten eyes of 10 patients with macular hole with (4 eyes) or without (6 eyes) retinal detachment in high myopia (axial length more than 26.5 mm) were treated by PPV with inverted ILM flap technique. RESULTS: Macular hole closure was observed in 8 eyes (80%) following the initial surgery (in 5 eyes without retinal detachment and in 3 eyes with retinal detachment). In 4 eyes with retinal detachment caused by macular hole, retinas of 3 eyes were reattached by the initial surgery. Postoperative best-corrected visual acuity improved by more than 2 lines in 5 eyes (50%), was unchanged in 4 eyes (40%), and worsened by more than 2 lines in 1 eye (10%). CONCLUSIONS: Inverted ILM flap technique might contribute to a high closure rate of macular hole and be a preferable adjuvant to the treatment of macular hole in high myopia with or without retinal detachment.

Inferior alveolar nerve paresthesia relieved by microscopic endodontic treatment.

We experienced two cases of inferior alveolar nerve paresthesia caused by root canal medicaments, which were successfully relieved by microscopic endodontic treatment. In the first case, the paresthesia might have been attributable to infiltration of calcium hydroxide into the mandibular canal through the root canals of the mandibular left second molar tooth. In the second case, the paresthesia might have been attributable to infiltration of paraformaldehyde through the root canals of the mandibular right second molar tooth. The paresthesia was relieved in both cases by repetitive microscopic endodontic irrigation using physiological saline solution in combination with oral vitamin B12 and adenosine triphosphate.