Functional Outcomes and Quality of Life After Sacrum Fractures Managed by Either Operative or Conservative Approaches: A Case Series With One-Year Follow-Up.

Background Pelvic fractures caused by high-energy trauma, such as motor vehicle accidents or falls from a considerable height, commonly lead to sacral fractures. Approximately a quarter of sacral fractures are linked to neurological injury, and overlooking these fractures may result in neurological issues such as sexual dysfunction, hindered lower limb functionality, and urinary and rectal difficulties. The main goal of this study is to introduce our patient group who underwent either operative or nonoperative treatment for sacral fractures, with a follow-up period of one year, and assess their functional outcomes. Methodology This is a retrospective review of prospectively collected data from a consecutive series of patients at the Apex Trauma Centre, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow. A consecutive series of 24 patients (17-55 years old) with sacral fractures treated either operatively or nonoperatively from 2018 to 2023 was studied. A total of 20 patients were available for follow-up questionnaires, and 20 patients participated in a physical examination. Time to final follow-up averaged 27.19 months (range = 12-57 months). The personal data of each patient was collected, including gender, age, comorbidities, concomitant injuries, mechanism of injury, fracture pattern/classification, surgical or nonsurgical treatment, other surgeries, length of surgery, length of hospital stays, adverse events, complications, neurologic and/or motor deficits, bowel and bladder function, and mortality. At a minimum one-year follow-up, the Majeed score, Oswestry Disability Index (ODI) questionnaire, and Gibbon's classification were assessed. Results All fractures were healed. Five patients showed neurological weakness, with three patients having only paresthesia and two patients having lower limb weakness. The mean Majeed score was 75.4, representing a moderate clinical outcome. Final ODI scores averaged 10.6, representing mild disability among patients with sacrum fractures. Overall, 40% of sacrum fractures were associated with sexual dysfunction, with 30% of females and 50% of males reporting this issue. There was no significant difference (p > 0.05) between operated and conservatively managed sacrum fractures concerning ODI scores, neurological deficit, and sexual dysfunction. Conclusions Both male and female patients with traumatic sacrum fractures experienced a significant decrease in their quality of life and sexual function at least 12 months after their surgery. Sacrum fractures are associated with an increased prevalence of sexual dysfunction and bowel/bladder incontinence. Our study findings indicate that patients with sacrum fractures experience similar functional outcomes and incidences of sexual dysfunction irrespective of whether they are managed operatively or conservatively.

A novel hemolytic complement-sufficient NSG mouse model supports studies of complement-mediated antitumor activity in vivo.

Monoclonal antibodies (mAbs) have emerged as a mainstream therapeutic option against cancer. mAbs mediate tumor cell-killing through several mechanisms including complement-dependent cytotoxicity (CDC). However, studies of mAb-mediated CDC against tumor cells remain largely dependent on in vitro systems. Previously developed and widely used NOD-scid IL2rγnull (NSG) mice support enhanced engraftment of many primary human tumors. However, NSG mice have a 2-bp deletion in the coding region of the hemolytic complement (Hc) gene, and it is not possible to evaluate CDC activity in NSG mice. To address this limitation, we generated a novel strain of NSG mice-NSG-Hc1-that have an intact complement system able to generate the membrane attack complex. Utilizing the Daudi Burkitt's human lymphoma cell line, and the anti-human CD20 mAb rituximab, we further demonstrated that the complement system in NSG-Hc1 mice is fully functional. NSG-Hc1 mice expressed CDC activity against Daudi cells in vivo following rituximab treatment and showed longer overall survival compared with rituximab-treated NSG mice that lack hemolytic complement. Our results validate the NSG-Hc1 mouse model as a platform for testing mechanisms underlying CDC in vivo and suggest its potential use to compare complement-dependent and complement-independent cytotoxic activity mediated by therapeutic mAbs.

Intratumoral localization and activity of 17ß-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer: a potent prognostic factor.

BACKGROUND: Estrogens were recently demonstrated to be synthesized in non-small cell lung carcinomas (NSCLCs) via aromatase activity and aromatase inhibitor (AI) did suppressed estrogen receptor (ER) positive NSCLC growth. However, other enzymes involved in intratumoral production and metabolism of estrogens, i.e. 17ß-hydroxysteroid dehydrogenases (i.e. 17ßHSD1 and 17ßHSD2) and others have not been studied. Therefore, in this study, we examined the clinical/ biological significance of 17ß-hydroxysteroid dehydrogenases in NSCLCs. METHODOLOGY: Archival materials obtained from 103 NSCLC patients were immunohistochemically evaluated using anti-17ßHSD1 and anti-17ßHSD2 antibodies. The findings of immunohistochemistry were then correlated with intratumoral estrone (E1) and estradiol (E2) concentration, clinicopathological factors and overall survival of the patients. We further employed NSCLC cell lines, A549 and LK87 to study the functional significance of 17ßHSD1, in vitro. RESULTS: A higher 17ßHSD1 immunoreactivity tended to be positively associated with aromatase (p=0.057) and tumor stage (p=0.055) whereas a higher 17ßHSD2 immunoreactivity was positively associated with a squamous cell and adenosquamous cell carcinomas subtypes (p=0.031), tumor stage (p=0.004), T factor of TNM classification (p=0.010), maximum tumor diameter (p=0.002) and tended to be associated with N factor of TMN classification (p=0.065). A higher 17ßHSD1 immunoreactivity was also significantly associated with lower intratumoral E1 concentration (p=0.040) and a higher intratumoral E2/E1 concentration ratio (p=0.028). On the other hand a higher 17ßHSD2 immunoreactivity was significantly associated with higher intratumoral E1 concentration (p=0.035). Results of multivariate regression analysis demonstrated an increased 17ßHSD1 immunoreactivity in tumor cells as an independent negative prognostic factor (HR= 2.83, p=0.007). E1 treatment in 17ßHSD1 positive NSCLC cells, A549 and LK87, resulted in E2 production (p<0.0001) and enhanced cell proliferation, which was abrogated effectively by 17ßHSD1 siRNA knockdown (p<0.0001). In addition, aromatase inhibitor treatment resulted in 17ßHSD1 up regulation in both A549 and LK87 cells. CONCLUSION: Results of our present study suggest that 17ßHSD1 may be considered an important prognostic factor in NSCLC patients and targeting 17ßHSD1 activity may further improve the clinical response in estrogen responsive NSCLC patients.

Sex steroid receptors in human lung diseases.

Several epidemiological studies have reported that gender differences exist in clinical and biological manifestations of human lung diseases. In particular, women are far more likely to develop both neoplastic and non-neoplastic lung diseases than men. This gender difference above suggests that sex steroid may be involved in the pathogenesis of various lung diseases. These sex steroids mediate their effects through sex steroid receptors including estrogen receptors (ER) i.e. ERα and ERß progesterone receptors (PR) i.e. PR-A and PR-B and androgen receptors (ARs), all of which have been reported to be expressed in lung tissue. Therefore it becomes important to clarify the potential roles of sex steroid receptor in both neoplastic and non-neoplastic lung diseases toward improved treatment options for the patients. In this review, we summarized a number of studies in humans and experimental animals that have identified possible roles of sex steroids in respiratory physiology and pathology.

Aromatase in human lung carcinoma.

Lung cancer is the leading cause of cancer mortality in both women and men worldwide but gender differences exist in their clinical and biological manifestations. In particular, among life time non-smoker, female are far more likely to develop lung carcinoma than male. Recent studies demonstrated that estrogens are synthesized in situ in both male and female lung cancers through aromatase, suggesting that sex steroid may contribute to the pathogenesis and development of lung carcinoma. In addition, human lung carcinomas have been recently demonstrated to be frequently associated with expression of estrogen receptors in both male and female patients and a lower expression of aromatase was reported to be associated with better prognosis. Preclinical studies further demonstrated that aromatase inhibitor (AI) suppressed the lung tumor growth both in vitro and in vivo. These findings all suggest a potential role of intratumoral aromatase in biological behavior of non-small cell lung cancer (NSCLC), the most common form of human lung malignancy. Therefore, AIs may become viable therapeutic options for disease management in NSCLC patients but further studies are definitely required to obtain a better understanding of the potential roles of intratumoral aromatase expression as a predictive biomarker for clinical outcome in these NSCLC patients.