BACKGROUND

The benefits of preimplantation genetic testing for aneuploidy (PGT-A) in the advanced maternal age group are unclear.

This study aims to determine whether PGT-A improves pregnancy outcomes.

This is a retrospective cohort study of PGT-A outcomes using next generation sequencing for advanced maternal age women undergoing IVF at CARMI from May 2017 to May 2021. Women were grouped by age: those 35-39 and those 40 and above. Pregnancy rate (PR), live birth rate (LBR), and miscarriage rate (MR) were computed per transfer and per cycle and compared with women who underwent single day-5 frozen transfer of a morphologically chosen embryo.

Overall euploid blastocyst rate was 38.5%: 16.9% for 40 and above and 47.6% for 35- 39 group. There were no transfers in 41.4% due to absence of a euploid embryo. PR and LBR per embryo transfer were higher in the PGT-A versus the non-PGT-A group (61.9% vs 24.1% p = < 0.001 and 42.9% vs 19% p = < 0.001). By age, the findings were similar: higher PR and LBR per-embryo transfer in PGT-A versus non-PGT-A in the 35-39 group (58.4% and 29%, p = 0.006 and 42.9% vs 22.6%, p < 0.001 respectively) and 40 and above (71.4% vs 18.5%, p < 0.001 and 53.6% vs 14.8%, p < 0.001 respectively). MR was increased in the PGT-A versus non-PGT-A group, but this may be due to the small number of events in the population.

The study suggests an increase in PR and LBR per embryo transfer in advanced maternal age women undergoing PGT-A. A larger sample size is needed to validate the results.

Parathyroid carcinoma is a rare endocrine malignancy with an indolent course but a high risk of recurrence. Diagnosis remains challenging, requiring integration of clinical, biochemical, radiologic, and histopathologic findings. We report a young patient presenting with primary hyperparathyroidism complicated by multiple pathologic fractures and chronic renal failure. Despite initial surgical and medical management, late aggressive recurrence occurred, resulting in significant systemic complications. This case highlights the need for vigilant long-term surveillance and improved diagnostic and therapeutic strategies.

Introduction: Pituitary stalk interruption syndrome (PSIS) is a rare congenital disorder characterized by the neuroradiological triad of an absent or interrupted pituitary stalk, ectopic posterior pituitary, and anterior pituitary hypoplasia. It is typically diagnosed in infancy or childhood due to growth failure or delayed puberty. Diagnosis in adulthood is uncommon and may occur after decades of untreated hypopituitarism. Case: A 34-year-old Malay male with underlying physical and intellectual disability presented after a mechanical fall resulting in left slipped capital femoral epiphysis, an unusual pathological fracture in adulthood. Clinical examination revealed marked infantilism with complete absence of secondary sexual characteristics (Tanner stage I). Laboratory evaluation demonstrated combined pituitary hormone deficiency, including severe central hypothyroidism, profound hypogonadotropic hypogonadism, and central adrenal insufficiency. Growth hormone and insulin-like growth factor 1 were undetectable, while prolactin was mildly elevated, consistent with pituitary stalk disruption due to loss of hypothalamic dopaminergic inhibition. Bone age assessment showed severe delay, corresponding to 15 years. Pituitary magnetic resonance imaging demonstrated the classical PSIS triad: anterior pituitary hypoplasia with partial empty sella, a high T1 signal nodule at the median eminence representing ectopic posterior pituitary, and non-visualization of the infundibulum, consistent with an absent pituitary stalk. Birth history revealed premature breech delivery, a recognized perinatal risk factor. The patient was commenced on hormone replacement therapy, including levothyroxine, hydrocortisone, testosterone undecanoate, and calcium–vitamin D supplementation. Conclusion This case illustrates that PSIS may remain undiagnosed into adulthood, leading to severe consequences of long-standing hypopituitarism such as osteoporosis and pathological fractures. Clinicians should consider hypopituitarism in adults presenting with unexplained fractures and delayed sexual maturation, particularly when supported by a suggestive perinatal history.
Fractures, Spontaneous ; Pituitary Gland

INTRODUCTION: Out-of-hospital-cardiac-arrest (OHCA) is a major public health challenge and post-return-of-spontaneous-circulation (ROSC) goals have shifted from just survival to survival with intact neurology. Although post-ROSC care is crucial for survival with intact neurology, there are insufficient well-established protocols for post-resuscitation care. We aimed to evaluate post-resuscitation care in the emergency department (ED) of adult (aged ≥16 years) OHCA patients with sustained ROSC and its associated neurologically intact survival. METHODS: A retrospective review of electronic medical records was conducted for OHCA patients with sustained ROSC at the ED. Data including demographics, pre-hospital resuscitation, ED resuscitation, post-resuscitation care and eventual outcomes were analysed. RESULTS: Among 921 OHCA patients, 85 (9.2%) had sustained ROSC at the ED. Nineteen patients (19/85, 22.4%) survived, with 13 (13/85, 15.3%) having intact neurology at discharge. Electrocardiogram and chest X-ray were performed in all OHCA patients, whereas computed tomography (CT) was performed inconsistently, with CT brain being most common (74/85, 87.1%), while CT pulmonary angiogram (6/85, 7.1%), abdomen and pelvis (4/85, 4.7%) and aortogram (2/85, 2.4%) were done infrequently. Only four patients (4.7%) had all five neuroprotective goals of normoxia, normocarbia, normotension, normothermia and normoglycaemia achieved in the ED. The proportion of all five neuroprotective goals being met was significantly higher ( P = 0.01) among those with neurologically intact survival (3/13, 23.1%) than those without (1/72, 1.4%). CONCLUSION Post-resuscitation care at the ED showed great variability, indicating gaps between recommended guidelines and clinical practice. Good quality post-resuscitation care, centred around neuroprotection goals, must be initiated promptly to achieve meaningful survival with intact neurology.
Humans ; Out-of-Hospital Cardiac Arrest/mortality* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Emergency Service, Hospital ; Cardiopulmonary Resuscitation/methods* ; Return of Spontaneous Circulation ; Aged ; Adult ; Treatment Outcome ; Electrocardiography ; Tomography, X-Ray Computed ; Aged, 80 and over

OBJECTIVES: Chromosomal abnormalities are the most common cause of spontaneous abortion (SA). This study aims to analyze the association between SA and chromosomal abnormalities in products of conception, and to compare the impact of different pregnancy modes and different numbers of previous abortions on chromosomal abnormalities, providing clinical consulting references. METHODS: A total of 1 345 SA patients treated at the Affiliated Women's Hospital of Jiangnan University (Wuxi Maternity and Child Health Care Hospital) between January 2019 and December 2023 were enrolled. According to the mode of conception, patients were divided into 2 groups: a spontaneous pregnancy group (S group, n=1242) and an assisted reproductive technology (ART)-conceived group (ART group, n=103). Based on the number of miscarriages, the S group was further subdivided into a spontaneous sporadic abortion group (S-1 group, n=780) and a spontaneous recurrent abortion group (S-2 group, n=462); the ART group was subdivided into an ART sporadic abortion group (ART-1 group, n=68) and an ART recurrent abortion group (ART-2 group, n=35). Chromosomal microarray analysis (CMA) was performed on products of conception. RESULTS: The incidence of numerical chromosomal abnormalities was 56.79% (443/780) in the S-1 group and 52.38% (242/462) in the S-2 group, while the incidence of structural abnormalities was 4.36% (34/780) and 7.36% (34/462), respectively. There was a statistically significant difference in structural abnormalities between the 2 groups (P<0.05). Among the spontaneous pregnancy SA cases, the incidence of numerical abnormalities decreased with increasing numbers of miscarriages, and was significantly lower in the group with ≥4 miscarriages compared to those with 1 or 2 miscarriages (both P<0.05). The incidence of structural abnormalities in groups with 1, 2, 3, and ≥4 miscarriages was 3.46%, 5.65%, 5.88%, and 4.35%, respectively, with no statistically significant differences among groups (all P>0.05). The incidence of pathogenic copy number variants (pCNVs) plus likely pathogenic copy number variants (LP-CNVs) gradually increases in the group with 1-3 miscarriages, and there was a statistically significant difference between the group with 1 miscarriage and the group with 2 miscarriages (P<0.05). In the ART group, the incidence of numerical abnormalities was 47.06% (32/68) in ART-1 and 37.14% (13/35) in ART-2, while structural abnormalities occurred in 2.94% (2/68) and 11.43% (4/35), respectively, with no significant differences between the groups (both P>0.05). There were no statistically significant differences in the incidence of numerical or structural abnormalities between the S-1 and ART-1 groups, or between the S-2 and ART-2 groups (all P>0.05). CONCLUSIONS Chromosomal numerical and structural abnormalities are common in SA patients from both spontaneous and ART-conceived pregnancies. Attention should be paid to patients with recurrent miscarriage in genetic investigation.
Humans ; Female ; Pregnancy ; Chromosome Aberrations/statistics & numerical data* ; Abortion, Spontaneous/epidemiology* ; Adult ; Reproductive Techniques, Assisted/adverse effects* ; Abortion, Habitual/genetics* ; Fertilization

Objective:To compare the changes in distortion product otoacoustic emission （DPOAE） test results in clinical patients with negative middle ear pressure after equalizing the pressure in the external canal and the middle ear cavity. This study aims to analyze the effect of negative middle ear pressure on otoacoustic emissions and investigate the correlation between the degree of negative middle ear pressure and the changes in amplitude and signal-to-noise ratio of DPOAE. Methods:Twenty-seven clinical patients were included, with 34 ears exhibiting negative middle ear pressure. Acoustic conductance tests, pure tone hearing threshold tests, and DPOAE tests were conducted under ambient pressure and peak pressure after equalizing the middle ear pressure for all tested ears. The amplitude and signal-to-noise ratio of DPOAE before and after compensating for middle ear pressure were recorded and statistically analyzed. Results:At 1.0 k Hz, 1.5 k Hz, and 8.0 k Hz, the DPOAE amplitude under ambient pressure was significantly higher than that under negative pressure （P<0.05）. A significant difference in the DPOAE signal-to-noise ratio was observed at 1.0 k Hz and 8.0 k Hz （P<0.05）. The difference in both amplitude and signal-to-noise ratio between these two test conditions was more pronounced at 1.0 k Hz （P<0.01）. There was no correlation between the negative pressure value from the tympanogram and the change in amplitude, with a weak negative correlation trend observed only at 0.75 k Hz （r=-0.328, P=0.054）. However, a significant negative correlation was found between the negative pressure value from the tympanogram and the change in signal-to-noise ratio at 0.75 k Hz （r=-0.366, P<0.05）. Conclusion:Compensating for middle ear pressure significantly improves the amplitude and signal-to-noise ratio of DPOAE in cases of negative middle ear pressure, particularly in the medium-frequency range. The smaller the degree of negative pressure in the middle ear, the weaker the effect of equalizing middle ear pressure is, especially in the low-frequency range.
Humans ; Ear, Middle/physiopathology* ; Male ; Female ; Adult ; Otoacoustic Emissions, Spontaneous ; Young Adult ; Middle Aged ; Pressure ; Adolescent ; Aged ; Signal-To-Noise Ratio

Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.
Humans ; Trophoblasts/physiology* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Pregnancy ; Abortion, Spontaneous/metabolism* ; Cell Line ; Placentation/genetics*

Pathological fractures after jaw cyst surgery are rare clinically but are a serious complication. Once a pathological fracture occurs, treatment time and economic costs increase, and doctors face difficulty in handling it. This article reports a case of a patient with mandibular pathological fractures after multiple odontogenic keratocyst surgery of the jaw. Mandibular lesions were located in the bilateral mandibular angles and had macrocystic changes. We adopted a conservative treatment plan, and the treatment effect was good. We also discussed and analyzed relevant literature to provide a reference for clinicians.
Humans ; Odontogenic Cysts/surgery* ; Conservative Treatment ; Postoperative Complications/therapy* ; Mandibular Fractures/etiology* ; Fractures, Spontaneous/etiology* ; Male ; Female

Introduction: Autoimmune polyendocrine syndrome (APS) type 4 is a clustering of at least 2 or more organ-specific autoimmune diseases in a single patient, which do not fall into other categories of APS, in combination with at least one more endocrine or non-endocrine organs. The multitude of autoimmune comorbidities and their associated treatment may contribute to osteoporosis and fracture. Case Description: A 35-year-old female with bilateral distal femoral pathologic fracture from an inch fall underwent bilateral, minimally invasive plate osteosynthesis. Pathologic fracture from secondary osteoporosis resulted from rheumatoid arthritis, chronic steroid use from rheumatoid arthritis (prednisone 10 mg for 24 months), premature ovarian failure since 20 years old without hormone replacement therapy, and possible Turner syndrome. She had persistently elevated thyroid-stimulating hormone in spite of high levothyroxine (4.25 μg/kg/day) dose; hence, gastric malabsorption from possible atrophic gastritis was likewise considered. Benefits and risks associated with treatment were reviewed to manage the patient holistically. Conclusion APS is a rare complex syndrome which may lead to various complications. Presence of hypogonadism, rheumatoid arthritis, and chronic steroid use further predisposes the development of secondary osteoporosis. Early screening and treatment of osteoporosis would have decreased the risk of development of fracture.
Fractures, Spontaneous ; Primary Ovarian Insufficiency ; Arthritis, Rheumatoid

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
Mice ; Animals ; Otoacoustic Emissions, Spontaneous/physiology* ; Hearing/physiology* ; Ear, Inner ; Hearing Loss/therapy* ; Genetic Therapy ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Membrane Proteins