Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis.

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor ß1, adipsin, fetuin-A, interleukin-1 ß, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.

Identifying women 45 years and younger at elevated risk for endometrial hyperplasia or cancer.

OBJECTIVE: To estimate the prevalence of, and identify risk factors associated with, endometrial hyperplasia and/or cancer (EH/EC) in patients ≤45 years old undergoing endometrial sampling for abnormal uterine bleeding (AUB). METHODS: We performed a retrospective cohort study of patients 18-45 years old with AUB who underwent endometrial sampling between 2016 and 2019 within a US-based multi-hospital system using billing code queries. We used multivariable Poisson regression to identify factors associated with EH/EC and calculated prevalence stratified by these factors. We estimated predicted probabilities within combinations of characteristics in order to examine the range of risk in this population. RESULTS: Among 3175 patients, median age was 39 years (interquartile range [IQR]:35-43) and BMI was 29.7 kg/m2 (IQR: 24.2-36.9). Thirty-nine percent were non-Hispanic White, 41% non-Hispanic Black, 9% Hispanic, and 11% Asian/Other/Unknown. BMI and polycystic ovarian syndrome (PCOS) were associated with higher EH/EC risk; non-Hispanic Black race was associated with lower risk. EH/EC prevalence ranged from 2% in BMI <25 to 16% in BMI ≥50 kg/m2 (p-trend <0.001). These prevalence estimates differed by race/ethnicity with the lowest estimates in non-Hispanic Black patients (0.5% BMI <25 vs. 9% BMI ≥50) and highest in Hispanic patients (1.5% BMI <25 vs. 33% BMI ≥50). Accounting for combinations of risk factors, predicted probabilities were highest - 34-36% - among patients with PCOS, diabetes, BMI ≥50, and Hispanic or Asian/Other/Unknown race/ethnicity. CONCLUSIONS: When accounting for combinations of key risk factors, risk of EH/EC in patients ≤45 years old with AUB ranges widely; the more nuanced estimates of risk presented here could help inform clinical decision-making about endometrial sampling in this population.

Treatment of vulvar and vaginal dysplasia: plasma energy ablation versus carbon dioxide laser ablation.

OBJECTIVE: Plasma energy ablation vaporizes tissues similar to carbon dioxide laser ablation, but is not hindered by the unique hazards and regulation of laser technology. We aimed to evaluate the complication rate and effectiveness of plasma versus laser ablation in the treatment of vulvovaginal high-grade squamous intra-epithelial lesions (HSIL). METHODS: We performed a retrospective cohort study of women treated with plasma or carbon dioxide laser ablation for histologically proven HSIL of the vulva or vagina from January 2014 to October 2019 at a single institution. Demographic factors, surgical characteristics, and complications were compared by ablation type using Fisher's exact tests. Recurrence-free survival was evaluated by ablation type using Kaplan-Meier curves, weighted log-rank tests, and Cox proportional hazards ratio estimates. RESULTS: Forty-two women were included; 50% underwent plasma and 50% underwent carbon dioxide laser ablation. Demographic factors were similar between the groups. 50% (n=21) were immunosuppressed, 45.2% (n=19) had prior vulvovaginal HSIL treatment, and 35.7% (n=15) were current smokers. Most women (n=25, 59.5%) were treated for vulvar HSIL, 38.1% (n=16) for vaginal HSIL. Complication rates did not differ by treatment: 9.5% (n=2) for laser ablation versus 4.8% (n=1) for plasma ablation (p=1.0). Over a median follow-up time of 29.3 months (IQR 11.0-45.0 months), recurrence rates were similar: 28.6% in the laser ablation group versus 33.3% in the plasma ablation group (weighted log rank p=0.43; 24-month HR 0.54, 95% CI 0.15 to 2.01). CONCLUSION: Plasma energy ablation of vulvovaginal HSIL has similar complication rates and recurrence risk to carbon dioxide laser ablation. This technique could be considered as an alternative treatment modality for vulvovaginal HSIL and warrants further investigation.

Outcomes following Craniosynostosis Surgery at a Tertiary Care Center in the Middle East.

BACKGROUND: Despite advancements in craniosynostosis surgery, open surgical approaches remain crucial for the management of infants >6 months of age and in those with complex synostosis. The clinical features of craniosynostosis remain poorly characterized in the Middle East. This study sought to assess the clinical features and outcomes of infants undergoing craniosynostosis surgery at a tertiary care center in Lebanon. METHODS: A retrospective review was performed of all patients who underwent craniosynostosis surgery from December 2006 to December 2018 at the American University of Beirut Medical Center, Lebanon. Clinicodemographic characteristics, complications, and recurrence outcomes were recorded and evaluated using descriptive statistics. RESULTS: Thirty-five infants met the inclusion criteria, with a mean age of 9.0 ± 4.0 months. The most common site of suture involvement was metopic (28.6%), followed by unilateral coronal (25.7%), sagittal (20.0%), bicoronal (8.6%), and multiple sites (17.1%). Five patients (14.3%) had syndromic synostosis. Median estimated blood loss was 200 mL, and median volume of transfused packed red blood cells was 180 mL. Two patients (5.7%) experienced postoperative complications, including postoperative blood transfusion (n = 1)and wire protrusion requiring removal (n = 1). Three patients (8.6%) required reoperation: 2 (5.7%) for resynostosis and 1 for traumatic fracture repair. Caregivers of all patients reported high satisfaction with cosmetic outcomes 4 weeks postoperatively. CONCLUSIONS: With appropriate perioperative precautions, open craniosynostosis surgery can be performed with minimal complications, low recurrence rates, and satisfactory cosmetic outcomes. Additional population-level data are needed to better characterize craniosynostosis patterns and outcomes in the Middle East.

Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. METHODS: This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. RESULTS: One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p < .001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p < .001 and p = .024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84-6.67; p < .001) and OS (aHR 2.00, 95%CI 1.04-3.88; p = .039) compared to HER2-negative tumors. CONCLUSIONS: Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.

Managing Isolated Symphyseal and Parasymphyseal Fractures in Pediatric Patients.

BACKGROUND: Isolated symphyseal or parasymphyseal mandibular fractures can confer significant morbidity in children. However, this mandibular injury pattern has not been well-characterized in children. This study investigated isolated symphyseal/parasymphyseal mandibular fractures in pediatric patients. METHODS: This was a 29-year retrospective, longitudinal cohort study of pediatric patients who presented to a single institution with isolated symphyseal/parasymphyseal mandibular fractures. Patient data were abstracted from medical records and compared between patients of varying dentition stages. RESULTS: Fourteen patients met inclusion criteria during the study period, of whom 2 (14.3%) had deciduous dentition, 7 (50.0%) had mixed dentition, and 5 (35.7%) had permanent dentition. Patients with deciduous dentition were significantly more likely to receive soft diet or closed treatment with mandibulomaxillary fixation than open reduction and internal fixation when compared to patients with mixed or permanent dentition (p = 0.04). The post-treatment complication rate was 40% among all patients treated with open reduction and internal fixation, 16.7% among patients who underwent closed treatment with mandibulomaxillary fixation, and 75% amongst patients treated with soft diet (though 2 patients who received soft diet had permanent dentition and thus were inappropriately managed). The most common complication overall was malocclusion (20%). A treatment algorithm was proposed based on study data; adherence to the algorithm significantly decreased odds of complications (odds ratio: 0.03, 95% confidence interval:0.001-0.6). CONCLUSIONS: The etiology, management, and outcomes of children with isolated symphyseal or parasymphyseal mandibular fractures at our institution varied by dentition stage. The authors proposed a treatment algorithm in order to optimize outcomes of symphyseal/parasymphyseal mandibular fractures in this patient population.

Open Reduction, Internal Fixation of Isolated Mandible Angle Fractures in Growing Children.

BACKGROUND: Mandible angle fractures can result in significant, long-term morbidity in children. However, management of this particular mandibular fracture type is not well-characterized in the pediatric population. This study investigated isolated mandibular angle fractures in the pediatric patients. METHODS: This was a 30-year retrospective, longitudinal cohort study of pediatric patients presenting to a single institution with mandibular angle fractures. Patient data were abstracted from electronic medical records. Subgroup analyses were completed by dentition stage. RESULTS: Seventeen patients met inclusion criteria, of whom 6 (35.3%) had deciduous, 4 (23.5%) had mixed, and 7 (41.2%) had permanent dentition. Deciduous/mixed dentition patients with mobile, displaced fractures underwent ORIF, whereas those with nondisplaced fractures underwent treatment with soft diet. Among permanent dentition patients, most patients (71.4%) underwent ORIF regardless of fracture severity. The post-ORIF complication rate was 55.6%; no complications were reported after soft diet or closed treatment (Fischer exact: P = 0.05). The most common post-ORIF complication was alveolar nerve paresthesia (17.6%) and post-ORIF complication rates did not vary by age (deciduous: 16.7%, mixed: 25.0%, permanent: 42.9%, Fischer exact: P = 0.80). ORIF patients who received a single upper border miniplate had a lower complication rate (42.9%) than other plating methods (upper and lower miniplates-100%). Fracture severity was predictive of post-ORIF complications (odds ratio: 2.23, 95% confidence interval: 2.22-2.24, P < 0.0001). CONCLUSIONS: Isolated mandible angle fractures were relatively rare in children, and treatment requirements varied by injury severity and dentition stage. Although isolated angle fractures had substantial associated morbidity, this fracture pattern did not result in notable growth limitations/deformity.

Differences in Prediagnostic Serum Metabolomic and Lipidomic Profiles Between Cirrhosis Patients with and without Incident Hepatocellular Carcinoma.

Background: Early detection of hepatocellular carcinoma (HCC) is crucial for improving patient outcomes, but we lack robust clinical biomarkers. This study aimed to identify a metabolite and/or lipid panel for early HCC detection. Methods: We developed a high-resolution liquid chromatography mass spectrometry (LC-MS)-based profiling platform and evaluated differences in the global metabolome and lipidome between 28 pre-diagnostic serum samples from patients with cirrhosis who subsequently developed HCC (cases) and 30 samples from patients with cirrhosis and no HCC (controls). We linked differentially expressed metabolites and lipids to their associated genes, proteins, and transcriptomic signatures in publicly available datasets. We used machine learning models to identify a minimal panel to distinguish between cases and controls. Results: Among cases compared with controls, 124 metabolites and 246 lipids were upregulated, while 208 metabolites and 73 lipids were downregulated. The top upregulated metabolites were glycoursodeoxycholic acid, 5-methyltetrahydrofolic acid, octanoyl-coenzyme A, and glycocholic acid. Elevated lipids comprised glycerol lipids, cardiolipin, and phosphatidylethanolamine, whereas suppressed lipids included oxidized phosphatidylcholine and lysophospholipids. There was an overlap between differentially expressed metabolites and lipids and previously published transcriptomic signatures, illustrating an association with liver disease severity. A panel of 12 metabolites that distinguished between cases and controls with an area under the receiver operating curve of 0.98 for the support vector machine (interquartile range, 0.9-1). Conclusion: Using prediagnostic serum samples, we identified a promising metabolites panel that accurately identifies patients with cirrhosis who progressed to HCC. Further validation of this panel is required.

The Impact of Androgenic Alopecia on the Quality of Life of Male Individuals: A Cross-Sectional Study.

Background Hair plays a significant role in physical appearance and hair loss can profoundly affect self-esteem and mental health. Studies show that people with clinically obvious and undetectable hair loss may have dramatically decreased quality of life (QoL). This study investigated the impact of androgenic alopecia on the quality of life of male individuals in the Eastern Province of Saudi Arabia and their willingness to seek treatment. Methods In the eastern province of Saudi Arabia, a cross-sectional study was carried out among men identified with androgenic alopecia (AGA). A self-administered survey was disseminated among the patients through social media sites. The questionnaire includes fundamental demographic factors including age, place of residence, level of education, the severity of androgenic alopecia, treatment method, and Skindex-29 to assess the patient's quality of life. Results Four hundred-two male patients out of 717 participants were selected, and 158 (39.3%) were aged between 20 to 29 years old. Satisfaction with treatment medication was reported by 24 (19.5%) out of those who underwent treatment (n=123). Less effectiveness was the most common reason for treatment dissatisfaction (81, 81.8%). The overall mean Skindex-29 score was 23.2 (SD 19.6) out of 100 points. Younger age, suffering hair loss for a shorter duration, undergoing alopecia treatment, being diagnosed with alopecia by a medical doctor, and having a moderate level of AGA were the factors that greatly affected the patient's QoL. Conclusion Consistent with the literature, this study showed that AGA significantly impaired patients' QoL. Among QoL domains, the symptoms domain had a greater effect on patients than the emotions or functional domains. Younger males who were suffering recently from hair loss and were diagnosed with AGA by the medical doctor demonstrated greater QoL impairment than the rest of the patients. A multicenter study may result in a better representation of the impact of QoL in patients with AGA.

Malignancy Rates in Thyroid Imaging Reporting and Data System Category 3 (TI-RADS 3) Thyroid Nodules: A Retrospective Study.

Introduction Thyroid cancer, one of the most frequently diagnosed endocrine malignancies, has witnessed a discernible global surge, predominantly among young adults. The etiological spectrum of thyroid cancer ranges from genetic mutations to environmental triggers. The early and precise detection of thyroid nodules (TNs) is crucial, given their latent potential for malignancy. Thyroid Imaging Reporting and Data System (TI-RADS) is an evidence-based stratification tool designed to standardize the assessment of TNs. Within this system, nodules categorized as TI-RADS 3 present an intermediate risk of malignancy, thereby necessitating meticulous evaluation. The objective of this study is to investigate the rates of cancer within thyroid nodules classified as TI-RADS 3, to determine the accuracy and effectiveness of the TI-RADS classification system in predicting malignancy at this intermediate-risk level, and to improve the diagnostic process and management strategies for these nodules. Methods A retrospective study was carried out on patients diagnosed with TI-RADS-3 thyroid nodules at King Fahad Hospital, Al-Hufof, between January 2019 and May 2023. Data were extracted from electronic medical records and encompassed patient demographics, and clinical and pathological details. Statistical analyses were performed using SPSS software version 27.0.1 (IBM Corp., Armonk, NY) examining the relationship between clinical characteristics and biopsy outcomes. Results The study involved 162 participants, mostly females (82.1%), with a median age of 43 years. Thyroid nodule analysis revealed 92.0% benign and 8.0% malignant cases, with the most common nodule size ranging from 2 to 2.4 cm. No significant correlation was found between clinical characteristics and biopsy results, indicating neither age nor gender significantly predicts malignancy in thyroid nodules within this cohort. Conclusion The majority of TI-RADS 3 nodules at King Fahad Hospital were benign. Yet, relying solely on TI-RADS for clinical decisions is not advised. An integrated approach, encompassing TI-RADS gradings and other nodule features, is essential for balanced patient management between intervention and observation.

Noninvasive Management of Pediatric Isolated, Condylar Fractures: Less Is More?

BACKGROUND: The purpose of this study was to examine injury patterns in pediatric mandibular condylar fractures and to propose and evaluate the validity of an institutional treatment algorithm for such fractures. METHODS: A retrospective chart review was conducted on pediatric patients who presented to the authors' institution with isolated mandibular condylar fractures between 1990 and 2016. Patients were categorized by dentition, and information regarding demographics, injury characteristics, management, and complications was compiled. RESULTS: Forty-three patients with 50 mandibular condylar fractures were identified. Twelve patients (27.9 percent) had deciduous dentition, 15 (34.9 percent) had mixed dentition, and 16 (37.2 percent) had permanent dentition. The most common fracture pattern in all groups was diacapitular [n = 30 (60 percent)]; however, older groups showed higher rates of condylar base fractures and bilateral fractures (p = 0.029 and p = 0.011, respectively). Thirty-one patients (72.1 percent) were treated with nonoperative management, 10 (23.2 percent) with closed treatment and mandibulomaxillary fixation, and two (4.7 percent) with open treatment and mandibulomaxillary fixation; nonoperative treatment was more common in younger patients (p = 0.008). Management for 10 patients (23.2 percent) was nonadherent to the treatment algorithm. Eight patients had complications (18.6 percent). Common complications included temporomandibular joint ankylosis (n = 2) and malocclusion (n = 2). Although complications were seen in all groups, adherence to the algorithm was associated with an 81.8 percent reduction in odds of complications (p = 0.032). CONCLUSIONS: Nonoperative management has a low complication rate in deciduous children. Children with permanent/mixed dentition may undergo closed treatment and mandibulomaxillary fixation if they have malocclusion/contralateral open bite, significant condylar dislocation, and ramus height loss greater than 2 mm. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Combined Symphyseal and Condylar Fractures: Considerations for Treatment in Growing Pediatric Patients.

BACKGROUND: Combined symphyseal-condylar mandible fractures are relatively common but difficult to manage in children. This study investigated the cause and management of symphyseal-condylar fractures in pediatric patients. METHODS: This study presents a retrospective review and expert opinion of pediatric symphyseal-condylar mandibular fracture management at the authors' institution between 1990 and 2019. National data from the Healthcare Cost and Utilization Project Kids' Inpatient Database (2000 to 2016) were used to determine whether institutional data had national applicability. RESULTS: Twenty-one patients at the authors' institution met inclusion criteria. Of these patients, 26.7 percent of deciduous dentition patients underwent open reduction and internal fixation, 40 percent underwent closed treatment (maxillomandibular fixation), and 33.3 percent received a soft diet. All mixed dentition patients underwent open reduction and internal fixation or closed treatment; all permanent dentition patients underwent open reduction and internal fixation. The national database (n = 1708) demonstrated similar treatment patterns: most permanent dentition patients (88.7 percent) underwent open reduction and internal fixation, most mixed dentition patients (79.2 percent) underwent closed treatment, and among deciduous dentition patients, 53.5 percent patients received a soft diet; 38 percent received closed treatment. In this study, the overall posttreatment complication rate was 62.5 percent among open reduction and internal fixation patients, 14.3 percent among closed treatment patients, and 16.7 percent among patients treated with a soft diet. CONCLUSIONS: Symphyseal-condylar mandibular fractures were associated with substantial morbidity in children. The authors created a treatment algorithm to maximize outcomes in children who suffer from this challenging fracture pattern. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Prevalence of endometrial cancer symptoms among overweight and obese women presenting to a multidisciplinary weight management center.

Endometrial cancer rates are rising in parallel with the obesity epidemic. We aimed to determine the prevalence of endometrial hyperplasia or cancer (EH/EC) bleeding symptoms among at-risk women. We conducted a retrospective cohort study of overweight and obese women at a multidisciplinary weight management center who had completed a gynecologic/menstrual history questionnaire from May 2018 to October 2019. The primary outcome of any EH/EC symptom was defined as follows: in premenopausal women, any recent abnormal uterine bleeding (AUB); in postmenopausal women: any bleeding/discharge. The prevalence of EH/EC symptoms was compared by menopausal status using Fisher's exact tests, and multivariable regression identified independent factors associated with having EH/EC symptoms. A total of 103 women were included, and 4 (4%) had a history of EH/EC. Of the 84 (n = 82%) of women with no prior hysterectomy, 57% (n = 33/58) of premenopausal women reported any EH/EC symptom compared to 15% (n = 15/26) of postmenopausal women (p < 0.001). Two-thirds of symptomatic premenopausal women had two or more symptoms, most commonly heavy menses (49% (n = 25/51)) and irregular periods (39% (n = 17/44)). Sixty percent (n = 20/33) had discussed these with a gynecologist, and one third had undergone an endometrial biopsy. A history of polycystic ovarian syndrome (RR:1.72, 95% CI 1.24-2.38) was associated with EH/EC symptoms, while being postmenopausal was not (RR:0.32, 95%CI: 0.12-0.87). We demonstrate that EH/EC bleeding symptoms are prevalent in this at-risk population, but frequently are not discussed with gynecologists. Providers who care for obese women should ask about EH/EC symptoms, and provide prompt referrals to facilitate prevention and early detection of this cancer.

Aromatase inhibitor therapy in recurrent, estrogen-receptor positive uterine serous carcinoma: A case report.

•There is a critical need for therapeutic options in uterine serous carcinoma (USC).•A substantial proportion of USC cases express estrogen receptors (ER).•This report describes use of letrozole therapy in recurrent, ER-positive USC.•Zoledronic acid may enhance letrozole efficacy against hormone-sensitive tumors.•Aromatase inhibitors could be a potential treatment option in ER-positive USC.

Acute abdomen due to an infected urachal cyst in a 5-year-old female: case report.

The urachus is an embryonic tube that connects the upper portion of the bladder to the umbilicus, and obliterates normally during embryonic development stages forming the median umbilical ligament. Incomplete obliteration of this tube results in many anomalies such as congenital patent urachus, umbilical urachal sinus, vesicourachal diverticulum and urachal cyst. We report in this case a 5-year-old female presented to the Emergency, complaining of generalized abdominal pain, fever, vomiting, and constipation with no umbilical discharge. The clinical presentation accompanied by radiology investigations suggested a case of acute abdomen. We performed an exploratory laparotomy and found a mass above the bladder connected to the umbilicus; we excised the mass and sent a specimen to pathology that confirmed Urachal cyst. Urachal cyst is usually asymptomatic unless it is complicated; depending on our case, we recommend surgical management by complete excision for complicated urachal cyst.

Association Between Age and Patient-Reported Changes in Voice and Swallowing After Thyroidectomy.

OBJECTIVES: Despite intact recurrent laryngeal nerves, patient-reported voice and swallowing changes are common after thyroidectomy. The association between patient age or frailty status and these changes is unknown. The aim of this study was to evaluate the impact of age and frailty on the incidence of voice and swallowing alterations after thyroidectomy. METHODS: We performed an institutional review board (IRB)-approved retrospective review of consecutive patients who underwent total thyroidectomy with intraoperative recurrent laryngeal nerve (RLN) monitoring at a single institution between January 2014 and September 2016. Patients with RLN injury were excluded. After data extraction, a modified frailty index (mFI) was calculated for each patient. The association among risk factors, including age, mFI, prior history of neck surgery, frequent voice use, presence of malignancy or gastroesophageal reflux disease, and smoking status and reported voice and/or swallowing changes was examined. RESULTS: Of 924 patients undergoing thyroidectomy, 148 (16.0%) reported only changes in voice; 52 (5.6%) reported only difficulty in swallowing; and 26 (2.8%) reported changes with both voice and swallowing. On multivariate analysis, we found a significant increase in voice or swallowing alterations up to the age of 50 years (5% increased odds per year), after which these changes plateaued. We found that mFI was not associated with voice or swallowing changes. CONCLUSION: Age ≥ 50 years is independently associated with the development of voice or swallowing changes after thyroidectomy, despite intact RLN. Additional prospective studies are needed to validate these findings, further define this association, and identify risk factors for developing these changes. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:519-524, 2019.

Interplay between p53 and Ink4c in spermatogenesis and fertility.

The tumor suppressor p53, and the cyclin-dependent kinase inhibitor Ink4c, have been both implicated in spermatogenesis control. Both p53-/- and Ink4c-/- single knockout male mice are fertile, despite testicular hypertrophy, Leydig cell differentiation defect, and increased sperm count in Ink4c-/- males. To investigate their collaborative roles, we studied p53-/- Ink4c-/- dual knockout animals, and found that male p53-/- Ink4c-/- mice have profoundly reduced fertility. Dual knockout male mice show a marked decrease in sperm count, abnormal sperm morphology and motility, prolongation of spermatozoa proliferation and delay of meiosis entry, and accumulation of DNA damage. Genetic studies showed that the effects of p53 loss on fertility are independent of its downstream effector Cdkn1a. Absence of p53 also partially reverses the hyperplasia seen upon Ink4c loss, and normalizes the Leydig cell differentiation defect. These results implicate p53 in mitigating both the delayed entry into meiosis and the secondary apoptotic response that occur in the absence of Ink4c. We conclude that the cell cycle genes p53 and Ink4c collaborate in sperm cell development and differentiation, and may be important candidates to investigate in human male infertility conditions.

Octogenarians have worse clinical outcomes after thyroidectomy.

BACKGROUND: The rising proportion of older adults in the US population coupled with an increased prevalence of nodular thyroid disease will result in more thyroidectomies being performed. The aim of this study is to evaluate the clinical outcomes among older adults (age ≥65) undergoing thyroidectomy compared to younger adults (18-64). METHODS: This was a population-based study of adult thyroidectomy patients using the Premier Healthcare Database, 2005-2014. Discharge status, hospital length of stay (LOS), morbidity, and total patient charge were compared between younger adults and older adults in three different age groups: ≥65, ≥70, and ≥80 years old. RESULTS: Among 75,141 thyroidectomy patients, 15,805 (21.0%) patients were ≥65 years, 8834 (11.8%) were ≥70 years, and 1613 (2.2%) were ≥80 years. Patients ≥80 years were 2.6 times (aOR:2.58, 95%CI: 1.72-3.86; p < 0.001) more likely to be discharged to a home health organization than to be discharged to their residence and 1.6 times (aOR:1.61, 95%CI: 1.30-2.00; p < 0.001) more likely to have at least one complication. CONCLUSIONS: Age ≥80 is an independent predictor of worse clinical outcomes after thyroidectomy.