Germline Genetic Mutations in Adult Patients with Sarcoma: Insight into the Middle East Genetic Landscape.

Data on germline mutations in soft tissue and bone sarcomas are scarce. We sought to identify the prevalence of germline mutations in adult sarcoma patients treated at a tertiary cancer center. Newly diagnosed patients were offered germline genetic testing via an 84-gene panel. The prevalence of pathogenic germline variants (PGVs) and their association with disease-, and patient- related factors are reported. A total of 87 patients were enrolled, the median age was 48 (19-78) years, and 47 (54%) were females. Gastrointestinal stromal tumors (n = 12, 13.8%), liposarcoma (n = 10, 11.5%), and Ewing sarcoma (n = 10, 11.5%) were the main subtypes. A total of 20 PGVs were detected in 18 (20.7%) patients. Variants of uncertain significance, in the absence of PGVs, were detected in 40 (45.9%) patients. Young age (p = 0.031), presence of a second primary cancer (p = 0.019), and female gender (p = 0.042) were correlated with the presence of PGVs. All identified PGVs have potential clinical actionability and cascade testing, and eight (44.44%) suggested eligibility for a targeted therapy. Almost one in five adult patients with soft tissue and bone sarcomas harbor pathogenic or likely pathogenic variants. Many of these variants are potentially actionable, and almost all have implications on cancer screening and family counselling. In this cohort from the Middle East, younger age, presence of a second primary tumor, and female gender were significantly associated with higher PGVs rates. Larger studies able to correlate treatment outcomes with genetic variants are highly needed.

Can we triumph over locally advanced cervical cancer with colossal para-aortic lymph nodes? A case report.

BACKGROUND: Para-aortic lymph nodes (PALNs) are common sites for the regional spread of cervical squamous cell carcinoma (SCC). CASE SUMMARY: We report the case of a 36-year-old woman who presented with cervical SCC with multiple bulky PALNs, largest measured 4.5 cm × 5 cm × 10 cm. The patient was treated with radical intent with definitive chemoradiation using sequential dose-escalated adaptive radiotherapy, followed by maintenance chemotherapy. The patient achieved a complete response; she has been doing well since the completion of treatment with no evidence of the disease for 2 years. CONCLUSION: Regardless of the size of PALN metastases of cervical carcinoma origin, it is still treatable (with radical intent) via concurrent chemoradiation. Adaptive radiotherapy allows dose escalation with minimal toxicity.

Significance of Beta Human Chorionic Gonadotropin in Predicting Disease Progression in Uterine Leiomyosarcoma.

Uterine leiomyosarcoma is a high-grade sarcoma that might be associated with dismal outcome. There are no hematological markers that can be used to follow up the recurrence and/or progression of the tumor. We present a case of a 44-year-old female, who was diagnosed with uterine leiomyosarcoma. During her management course, serum beta human chorionic gonadotropin (ß-hCG) elevation was correlated with clinical and radiological disease progression on two separate occasions. This correlation should be further investigated to potentially integrate serum ß-hCG as a predictive tool for clinical behavior and treatment response.

Incidence, risk factors and outcomes of acute kidney injury in surgical intensive care unit octogenarians at the Jordan University Hospital.

BACKGROUND: Acute kidney damage (AKI) is among the most severe consequences observed in surgical intensive care units (SICUs). We aim to observe the incidence, risk factors, and outcomes of acute kidney injury in SICU octogenarians. METHODS: A cross-sectional retrospective study was conducted at the SICU of Jordan University Hospital (JUH), a tertiary teaching hospital in a developing country, between January 2018 and December 2019. Patients who were 80 years or older at the time of data collection were included. The definition of AKI was based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Demographic, clinical, and laboratory data were reviewed. RESULTS: A total number of 168 patients were included. The mean age was 84.0 ± 3.8 years, and 54.8% of the participants were women. Of those, 115 (68.5%) had surgery before or during ICU stay, and 28.7% of the patients' surgeries were an emergency surgery. Also, 47.8% of surgeries were considered by anesthesia to be high-risk surgeries. A total of 55 patients (32.7%) developed AKI during their SICU stay. The factors that were significantly associated with AKI in the ICU patients included use of beta blocker [AOR: 3.7; 95% CI: 1.2-11.8; p = 0.025], and inotropes [AOR:4.0; 95% CI: 1.2-13.3; p = 0.03]. The factors that were significantly associated with mortality in the ICU included using mechanical ventilation [AOR:18.7; 95% CI: 2.4-141.9; p = 0.005] and inotropes use [AOR: 12.3; 95% CI: 1.2-120.7; p = 0.031]. CONCLUSIONS: The incidence of AKI during SICU stay in this study was 32.7% and it was significantly associated with the use of beta blockers, mechanical ventilation, and inotropes. The mortality rate among octogenarians who developed AKI during SICU stay was 36.4%. Further studies are needed globally to assess the incidence of AKI in octogenarian surgical patients and identify risk factors to provide preventative measurements and strategies.

Effects of Smoking on Outcomes of Anti-Vascular Endothelial Growth Factor Therapy in Patients with Diabetic Macular Edema: A Retrospective Case-Control Study.

PURPOSE: To determine the effect of smoking on the response to anti-vascular endothelial growth factor (anti-VEGF) therapy treatment in patients with diabetic macular edema (DME). METHODS: This is a retrospective case - control study that included 60 eyes with DME. Smoking habits were obtained from hospital records and patient recall. Patients were divided into two groups: the ever-smoker group and the never-smoker group. All patients received Intravitreal ranibizumab with three loading doses followed by PRN protocol and all were followed up for at least 1 year. Outcome measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, and number of visits. RESULTS: Smoking was not associated with worse posttreatment visual acuity and was not found to influence the change in ocular coherence tomography measurement of central macular thickness and the change in BCVA (posttreatment minus pretreatment). There were no statistically significant differences in the duration of treatment or number of visits between two groups of patients the ever-smoker group and the never-smoker group (P > 0.05). CONCLUSION: In this study, smoking status did not influence the treatment outcome of anti-VEGFs; however, smoking should be encouraged due to its well-known other systemic unwanted effects.

Generation and characterization of induced pluripotent stem cell (iPSC) line (JUCTCi002-A) from a patient with ataxia with oculomotor apraxia type 1 (AOA1) harboring a homozygous mutation in the APTX gene.

Ataxia with Oculomotor Apraxia Type 1 (AOA1) is an autosomal-recessive cerebellar ataxia characterized by early-onset cerebellar atrophy and axonal sensorimotor polyneuropathy. AOA1 is related to mutations in the aprataxin (APTX) gene encoding for the aprataxin protein. The aprataxin protein has been reported to be involved in DNA single-strand break repair (SSBR) machinery and it localizes to the mitochondria to preserve the mitochondrial function. Here, we demonstrate the generation of induced pluripotent stem cell (iPSC) line (JUCTCi002-A) from AOA1 patient's skin dermal fibroblasts. The selected line showed normal karyotype, expression of pluripotency markers and the ability to differentiatie in vitro into the three germ layers.

Identification of APTX disease-causing mutation in two unrelated Jordanian families with cerebellar ataxia and sensitivity to DNA damaging agents.

BACKGROUND: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive cerebellar ataxia, caused by mutations in the APTX gene. The disease is characterized by early-onset cerebellar ataxia, oculomotor apraxia and severe axonal polyneuropathy. The aim of this study was to detect the disease-causing variants in two unrelated consanguineous Jordanian families with cerebellar ataxia using whole exome sequencing (WES), and to correlate the identified mutation(s) with the clinical and cellular phenotypes. METHODS: WES was performed in three affected individuals and segregation analysis of p.W279* APTX candidate variant was performed. Expression levels of APTX were measured in patients' skin fibroblasts and peripheral blood mononuclear cells, followed by western blot analysis in skin fibroblasts. Genotoxicity assay was performed to detect the sensitivity of APTX mutated cells to H2O2, MMC, MMS and etoposide. RESULTS: A recurrent homozygous nonsense variant in APTX gene (c.837G>A, p.W279*) was revealed in all affected individuals. qRT-PCR showed normal APTX levels in peripheral blood and lower levels in fibroblast cells. However, western blot showed the absence of APTX protein in patients' skin fibroblasts. Significant hypersensitivity to H2O2, MMC and etoposide and lack of sensitivity to MMS were noted. CONCLUSIONS: This is the first study to report the identification of a nonsense variant in the APTX gene (c.837G>A; p.W279*) in AOA1 patients within the Jordanian population. This study confirmed the need of WES to assist in the diagnosis of cerebellar ataxia and it emphasizes the importance of studying the pathophysiology of the APTX gene.