Catheter-related Infections in Pediatric Patients Due to a Rare Pathogen: Herbaspirillum huttiense.

BACKGROUND: Herbaspirillum species are nonfermenting, aerobic, helical or curved, Gram-negative bacteria belonging to the class Betaproteobacteria, order Burkholderiales. To date, only a few studies have reported on the epidemiology, clinical symptoms, antibiotic susceptibility profiles, treatment and outcomes of Herbaspirillum huttiense -related infections in pediatric patients. METHODS: The aim of this study was to present 3 years of H.huntiense data, antibiotic susceptibility profiles, systemic antibiotics and antibiotic lock therapy (ALT) options and clinical outcomes. RESULTS: Fourteen episodes of infection in 12 patients were included in this retrospective study. The patients had a male/female ratio of 1:1 and a median age of 160.5 months (range, 3-198 months). Catheter-related bloodstream infection (CRBSI) was detected in 11 patients. Only 1 patient developed catheter-related infective endocarditis. The patient's catheter was removed, and she was successfully treated with systemic antibiotics for 4 weeks. Systemic antibiotics were used in all infections related to H. huttiense . In septic, critically ill patients, the catheter was removed, and systemic antibiotics were started. Port catheters were removed in 5 patients. ALT was performed in clinically stable patients. ALT using amikacin was administered to 6 patients through the port catheter. Two patients had a 2nd attack. After the 2nd ALT treatment, 1 patient cured, and the catheter of the other patient was removed due to persistent microbial growth in cultures. Antimicrobial susceptibility testing of the reported isolates showed susceptibility to meropenem (90%), ceftazidime (87%) and piperacillin/tazobactam (65%), with 92% resistance to colistin. CONCLUSION: H. huttiense is an emerging pathogen in CRBSI. Piperacillin/tazobactam, ceftazidime and meropenem appear to be good therapeutic options for the treatment of H. huttiense infections. ALT and systemic antibiotics can be used in H. huttiense -CRBSI to sterilize and preserve the central venous catheter.

BRCA Mutations and MicroRNA Expression Patterns in the Peripheral Blood of Breast Cancer Patients.

Breast cancer (BC) persists as the predominant malignancy globally, standing as the foremost cause of cancer-related mortality among women. Despite notable advancements in prevention and treatment, encompassing the incorporation of targeted immunotherapies, a continued imperative exists for the development of innovative methodologies. These methodologies would facilitate the identification of women at heightened risk, enhance the optimization of therapeutic approaches, and enable the vigilant monitoring of emergent treatment resistance. Circulating microRNAs (miRNAs), found either freely circulating in the bloodstream or encapsulated within extracellular vesicles, have exhibited substantial promise for diverse clinical applications. These applications range from diagnostic and prognostic assessments to predictive purposes. This study aimed to explore the potential associations between BRCA mutations and specific miRNAs (miR-21, miR-155, miR-126, and miR-200c) expression that are known to be dysregulated in BC patient samples. Our findings indicate a robust correlation between miRNA expression status and disease subtypes. We found a correlation between the expression status of miRNAs and distinct disease subtypes. Intriguingly, however, no significant associations were discerned between disease status, subtypes, or miRNA expression levels and the presence of BRCA mutations. To advance the validation of miRNAs as clinically relevant biomarkers, additional investigations within larger and meticulously selected patient cohorts are deemed imperative. These microRNA entities hold the potential to emerge as groundbreaking and readily accessible tools, poised for seamless integration into the landscape of clinical practice.

A Randomized Comparison Between Interscalene and Combined Interscalene-Suprascapular Blocks for Arthroscopic Shoulder Surgery: A Prospective Clinical Study.

Background: To compare the analgesic effect of ISB with a combination of ISB-SSNB and patients who were given opioids with PCA without block in adult patients undergoing shoulder surgery, as measured by opioid consumption and pain intensity in the first 24 hours postoperatively. Methods: Ninety patients who underwent shoulder surgery were randomly divided into three groups. Group I in which ISB was performed and patient-controlled analgesia (PCA) was inserted, Group II with; ISB and SSNB combined, and PCA was inserted, and Group III where; only PCA was used. Visual analog scale (VAS) pain scores at the second, fourth, sixth, 12th, and 24th hours, morphine consumption, additional analgesic requirement, and patient satisfaction were evaluated. Results: Compared with Group III, the VAS pain score was significantly lower in Group I and Group II at 2, 4, 6, 12, and 24 hours postoperatively. In Group I, the VAS score at rest at the 6th hour was found to be higher than in Group II. The 24-hour total morphine consumption was higher in the control group than in Group I and Group II. The satisfaction score of the control group was lower than Group I and Group II. Conclusion: The combined application of ISB and SSNB block is beneficial in shoulder surgery to provide both intraoperative and postoperative analgesia and opioid consumption. Level of Evidence: Level I; Randomized Controlled Trial; Treatment Study.

The effect of oral hydroxychloroquine on chondral defect: An experimental study.

OBJECTIVES: This study aims to evaluate the time- and dose-dependent effects of oral hydroxychloroquine (HCQ) on focal full-thickness knee chondral defect healing in a rabbit model. MATERIALS AND METHODS: Cartilage defects of 4x4 mm2 were created on both medial femoral condyles of 24 New Zealand rabbits. The rabbits were divided into six groups (A-F) according to HCQ administration and sacrifice time: A (three-week control) and B (six-week control) received no additional interventions; C (20 mg/kg HCQ, three weeks); D (20 mg/kg HCQ, six weeks); E (40 mg/kg HCQ, three weeks); and F (40 mg/kg HCQ, six weeks). Osteochondral specimens were evaluated macroscopically, histologically, and immunohistochemically. The terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method was used to detect apoptotic cells. RESULTS: The International Cartilage Repair Society (ICRS) scores were significantly higher in the experimental groups than in the controls (p<0.001). The Wakitani scores in Group D showed a significant improvement compared to those in Group B (p<0.01). The 20 mg/kg HCQ treatment groups showed better recovery than the controls (p<0.01). High-dose HCQ (40 mg/kg) treatment significantly reduced the intensity of collagen type 2 immunoreactivity compared to that in the groups receiving 20 mg/kg of HCQ (p<0.01). Collagen type 2 expression in Group F was significantly lower than that in Group D (p<0.01). There were more TUNEL-positive cells in the repair sites of Groups E and F than in the lower-dose experimental groups and untreated experimental groups (p<0.001). CONCLUSION: A low dose of HCQ improved cartilage repair, while higher doses of HCQ exerted a negative effect on cartilage regeneration in rabbits. In the presence of defective cartilage, the use of HCQ at an appropriate dose and time is important for cartilage health.

Do parents vaccinated against COVID-19 protect their children from hospitalization due to COVID-19?

OBJECTIVE: This study aimed to determine whether parental vaccination against coronavirus disease 2019 (COVID-19) prevents hospitalization of COVID-19-infected children. METHODS: This study was based on data obtained from the records of pediatric patients that were followed up for virologically proven COVID-19 infection between August and October 2021, during which time the delta variant was dominant in Turkey and the children were isolating at home. RESULTS: There were 151 patients in the inpatient group and 218 in the outpatient group; the mean age was 172.5 and 145.5 months in the groups, respectively. The rates of obesity (22.5% and 6.4%, respectively, p < 0.001) and neurological-neurodevelopmental disorders (8.6% and 1.4%, respectively, p < 0.001) were significantly higher in the inpatient group than in the outpatient group. Of the outpatients' parents, 67.4% (n = 147) were fully vaccinated vs. 38.4% (n = 58) in the inpatient group. In all, 39.7% (n = 60) of the inpatients' parents were unvaccinated vs. 18.3% (n = 40) in the outpatient group. There was a significant correlation between the vaccination status and the patient groups (p < 0.001); it was determined that the COVID-19 infection would be mild in children if both parents were fully vaccinated. When both parents were fully vaccinated against COVID-19, the hospitalization rate decreased and the outpatient follow-up rate increased. CONCLUSION: Having both parents fully vaccinated against COVID-19 can indirectly protect their subsequently infected children from hospitalization and the long-term effects of infection. Nonetheless, more comprehensive research on delta and non-delta variants is needed.

The effect of biceps tenotomy on humeral migration and clinical outcomes in arthroscopic rotator cuff repair.

PURPOSE: To evaluate the effect of biceps tenotomy on humeral migration and clinical outcomes in patients who underwent arthroscopic rotator cuff (RC) repair. METHODS: This is a retrospective study of 60 patients who underwent arthroscopic RC repair. Patients were divided into two groups, whether they underwent concomitant biceps tenotomy or not. The group underwent concomitant biceps tenotomy, tenotomy ( +), or not, tenotomy (-). Clinical and functional outcomes were performed using the American Shoulder and Elbow Surgeons (ASES), the University of California-Los Angeles (UCLA) scoring system. Radiological evaluation was performed in X-rays and magnetic resonance imaging (MRI), measuring the acromiohumeral distance (AHD), humeral migration (HM) and upper migration index (UMI). RESULTS: There was no significant difference between the groups in terms of patient characteristics. The follow-up period was 30.9 ± 8.7 months in the tenotomy ( +) group and 34.9 ± 8.2 months in the tenotomy (-) group with no significant difference. Postoperative ASES score improved significantly in the tenotomy ( +) group compared to the tenotomy (-) group (91.2 ± 4.7, 80.8 ± 18.7, respectively, p = 0.005). There was a significant difference in postoperative AHD, HM and UMI values (MRI; p = 0.003, p = 0.017, p = 0.025; X-ray; p = 0.049, p = 0.002, p = 0.010, respectively). The post-pre difference increase of AHD [MRI for tenotomy( +): 0.14 ± 0.86 and tenotomy(-): 0.91 ± 0.85, p = 0.001; X-ray for tenotomy( +): 0.61 ± 0.43 and tenotomy(-): 1.12 ± 0.7, p = 0.001] and UMI [MRI for tenotomy( +): 0.005 ± 0.05 and tenotomy(-): 0.04 ± 0.06, p = 0.006; X-ray for tenotomy( +): 0.01 ± .064 and tenotomy(-): 0.12 ± 0.37, p = 0.110] values were higher in the tenotomy (-) group compared to the tenotomy ( +) group while HM values decreased more in the tenotomy (-) group. [MRI for tenotomy ( +): -0.19 ± 1.07 and tenotomy (-): -0.79 ± 1.52, p = 0.079; X-ray for tenotomy ( +): -0.27 ± 0.54 and tenotomy (-): -1.006 ± 1.83, p = 0.040]. CONCLUSION: After short-term follow-up, the humeral head was positioned higher in patients who underwent LHBT tenotomy compared to patients without tenotomy. However, it seems to affect clinical outcomes during this period positively. LEVEL OF EVIDENCE: Level 3.

Anatomic Factors Associated With the Development of an Anterior Cruciate Ligament Rerupture in Men: A Case-Control Study.

BACKGROUND: Although several factors are associated with anterior cruciate ligament (ACL) rerupture, the effect of anatomic factors associated with ACL rupture on ACL rerupture development has not been evaluated. PURPOSE: To determine individual anatomic parameters independently associated with ACL rerupture and the diagnostic values of these parameters. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 91 male patients with ACL rerupture and 182 age-, sex-, body mass index-, and side dominance-matched patients without rerupture who underwent ACL reconstruction with a 5-year follow-up were included. In all, 35 parameters that were previously defined as risk factors for primary ACL rupture were compared between the 2 groups. Uni- and multivariate logistic regression models were created to evaluate independently associated factors. Receiver operating characteristic curve analysis was performed for independently associated parameters to predict sensitivity, specificity, and cutoff values. RESULTS: The mean ± standard deviation age of patients at the time of index surgery was 26.5 ± 6.7 years. Notch shape index (P = .014), tibial proximal anteroposterior (AP) distance (TPAPD) (P < .001), lateral femoral condylar AP distance (LCAPD)/TPAPD ratio (P < .001), medial meniscal cartilage bone height (P < .001), and lateral meniscal bone angle (P = .004) were found to be significantly different between the 2 groups. Only the LCAPD/TPAPD ratio (odds ratio, 2.713; 95% CI, 1.998-5.480; P < .001) was found to be independently associated with ACL rerupture development. The LCAPD/TPAPD ratio revealed 78.9% sensitivity and 75.5% specificity (area under the curve, 0.815; 95% CI, 0.760-0.870) for values above 1.52. CONCLUSION: The LCAPD/TPAPD ratio can be used to distinguish patients who are at risk of developing ACL rerupture from patients who are not. In the clinical practice, findings of this study may help to develop surgical and nonsurgical preventive strategies in ACL rerupture development.

Assessment of clinical, biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study.

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 108 WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1ß, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid. Level of evidence: IV.

Multigene Panel Testing in Turkish Hereditary Cancer Syndrome Patients.

Objective: Hereditary cancer syndromes (HCSs) are a heterogenous group of disorders caused by germline pathogenic variations in various genes that function in cell growth and proliferation. This study aimed to describe the germline variations in patients with hereditary cancer using multigene panels. Methods: The molecular and clinical findings of 218 patients with HCS were evaluated. In addition, 25 HCS-related genes were sequenced using a multigene panel, and variations were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. In total, 218 HCS patients predominantly with breast, colorectal, ovarian, gastric, and endometrium cancers were included. Results: Pathogenic variations in 12 distinct genes were detected in 36 of 218 (16.5%) cases. In this study, the most affected gene was the ATM gene, in which pathogenic variations were detected in 8 of 218 cases, followed by CHEK2 (3.2%), MUTYH (3.2%), BRIP1 (1.8%), BARD1 (0.9%), TP53 (0.9%), PALB2 (0.4%), MLH1 (0.4%), MSH2 (0.4%), PMS2 (0.4%), RAD50 (0.4%), and RAD51C (0.4%). Conclusions: This study contributes to genotype-phenotype correlation in HCSs and expands the variation spectrum by introducing three novel pathogenic variations. The wide spectrum of the gene pathogenic variations detected and the presence of multiple gene defects in the same patient make the multigene panel testing a valuable tool in detecting the hereditary forms of cancer and providing effective genetic counseling and family specific screening strategies. Amaç: Herediter kanser sendromlari (HCS) hücre büyümesi ve proliferasyonunda görevli genlerde saptanan germline mutasyonlardan kaynaklanan heterojen bir grup hastaliktir. Bu çalismada kalitimsal kanser sendrom ön tanisiyla degerlendirilen olgularda çoklu gen paneli ile germ hatti varyasyonlarinin degerlendirilmesi planlanmistir. Yöntemler: Kalitimsal kanser sendromu düsünülen 218 olgudan periferik kandan DNA izolasyonu sonrasi HCS ile iliskili 25 gen multigen panel kullanilarak dizilendi ve varyasyonlar American College of Medical Genetics and Genomics (ACMG) kriterlerine göre degerlendirildi. Bulgular: Meme, kolorektal, over, gastrik ve endometriyum kanseri basta olmak üzere toplam 218 herediter kanser sendromlu olgu degerlendirildi. Tüm çalisma grubu incelendiginde en sik ATM gen varyasyonlari (8/218, %3,6) tespit edildi ve bunu siklik sirasina göre CHEK2 (%3,2), MUTYH (%3,2), BRIP1 (%1,8), BARD1 (%0,9), TP53 (%0,9), PALB2 (%0,4), MLH1 (%0,4), MSH2 (%0,4), PMS2 (%0,4), RAD50 (%0,4), RAD51C (%0,4) varyasyonlari takip etmekteydi. Sonuçlar: Bu çalismada farkli kanser türlerinde kalitimsal kansere yol açan genler analiz edilmis ve fenotiple iliskisi degerlendirilmistir. Ayrica bu çalismada ilk kez saptanan üç yeni varyasyon ile literatüre katki saglanmaktadir. Patojenik varyasyon tespit edilen genlerin genis dagilimi ve ayni hastada birden fazla genetik varyasyonun varligi düsünüldügünde, uygun genetik danisma ve aileye özgü tarama planlamasi yapmak için çoklu gen taramasi kalitimsal kanser hastalarinin degerlendirilmesinde hizli ve etkin bir yöntem olarak görünmektedir.

Mutation Spectrum of Familial Adenomatous Polyposis Patients in Turkish Population: Identification of 3 Novel APC Mutations.

BACKGROUND: Familial adenomatous polyposis (OMIM #175100) and MUTYH-associated polyposis (OMIM #608456) are rare cancerprone disorders characterized by hundreds of adenomatous polyps in the colon and rectum, which have a high probability of malignant transformation. Attenuated familial adenomatous polyposis is a variant of familial adenomatous polyposis, which is a term used for the condition in which patients have less than 100 colorectal polyps. Germline heterozygous Adenomatous polyposis coli (APC) and biallelic MUTYH (mutY DNA glycosylase) pathogenic variations are responsible for familial adenomatous polyposis and MUTYH-associated polyposis respectively. The aim of this study is to discuss the clinical manifestations of patients having pathogenic APC and MUTYH variations. METHODS: We included 27 probands who have more than 10 colonic polyps in this study. After evaluation of their clinical and family histories, the probands were screened for APC and MUTYH variations via next generation sequencing. The family members of the probands carrying pathogenic variations were screened via Sanger sequencing. RESULTS: Among 27 probands, pathogenic APC and MUTYH variations were detected in 3 and 6 probands respectively. In the APC gene, 3 novel truncating variations (p.Leu360*, p.Leu1489Phefs*23, and p.Leu912*) were detected in 3 unrelated probands. In the MUTYH gene, only 2 distinct pathogenic variations were detected (p.Pro295Leu and p.Glu480del) in the homozygous or compound heterozygous state. CONCLUSION: In this study, molecular etiology was clarified in 9 familial polyposis patients. The p.Pro295Leu and p.Glu480del variations seem to be common in the Turkish population and may be considered as a first-step genetic test in Turkish familial polyposis patients showing autosomal recessive inheritance. However more studies are needed to reveal the exact frequency of these variations.

Inhaled Dry Powder Mannitol Treatment in Pediatric Patients with Cystic Fibrosis: Evaluation of Clinical Data in a Real-World Setting.

Background: Cystic fibrosis (CF) is a genetic disorder, in which defective clearance of airway secretions leads to progressive lung function loss. Inhaled mannitol is used to increase sputum and mucociliary clearance. There are little data from real-world studies on the effectiveness of mannitol in children. Our objective was to evaluate the spirometry and clinical results of mannitol in pediatric patients. Methods: We retrospectively reviewed the records of 30 children and adolescents with CF receiving inhaled mannitol who were already on recombinant human deoxyribonuclease (rhDNase) treatment. The change in forced expiratory volume in 1 second (FEV1) from baseline at 2-4 months was the primary outcome. Secondary measures were other spirometry results, body mass index (BMI), hospital admissions, sputum characteristics, and positive bacterial colonization. Results: Compared to baseline, we found significant improvement in percent predicted FEV1 at 2-4 months of treatment; 84.50 (58.00-99.00) vs. 96.00 (66.00-106.00) (P = 0.0007). The absolute change in FEV1 was +11.5% at 2-4 months, +6.5% at 5-7 months, and +4% at 8-12 months. Also, significant improvements in other spirometry results were observed. Adolescents had significantly lower FEV1 results, but the improvement in their lung function was sustained for a more extended period than children. Mannitol provided easier sputum removal, increased sputum volume, significant decline in hospitalizations, and significantly fewer patients with positive sputum cultures. A significant increase in BMI at 8-12 months was observed. Cough was the most frequent adverse effect. Conclusion: In a real-world setting, our results demonstrated that adding mannitol to rhDNase therapy is tolerable in pediatric patients with CF and may provide improved spirometry and clinical outcomes. In addition, our results showed that mannitol provided recovery in overall lung function at 2-4 months, which was sustained up to 12 months together with improved BMI, easier sputum removal, and a decline in bacterial colonization and hospital admissions. However, cough was the most frequent side effect.

A Novel ATM Gene Mutation Affecting Splicing in an Ataxia-Telangiectasia Patient.

Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive ataxia, choreoathetosis and immunodeficiency beginning in early childhood. An 8-year-old girl was referred with a diagnosis of AT. She had gait disturbance and dysarthria for 3years. Multiple cutaneous telangiectases were observed on her face, trunk and limbs. Sequence analysis of the ATM gene revealed a homozygous c.7308-15A>G mutation in IVS49. Human Splicing Finder predicted that the mutation could activate an intronic cryptic acceptor site. We designed primers for amplification of related exons (48-50) from cDNA for evaluating splicing pattern. Sequencing of ATM exons 48-50 revealed a 14-nucleotide insertion from intron 49, between exons 49 and 50, resulting in premature termination of translation at codon 2439. To conclude, we report a novel mutation in a classical AT case, which resulted in an alternatively spliced transcript and was predicted to form a truncated protein or null protein due to nonsense-mediated decay.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

ABSTRACT Objetivo: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. Subjects and methods: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. Results: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. Conclusion: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.

Whole-exome sequencing reveals new potential genes and variants in patients with premature ovarian insufficiency.

PURPOSE: Premature ovarian insufficiency (POI) is a heterogeneous disorder characterized by the cessation of menstrual cycles before the age of 40 years due to the depletion or dysfunction of the ovarian follicles. POI is a highly heterogeneous disease in terms of etiology. The aim of this study is to reveal the genetic etiology in POI patients. METHODS: A total of 35 patients (mean age: 27.2 years) from 28 different families diagnosed with POI were included in the study. Karyotype, FMR1 premutation analysis, single nucleotide polymorphism (SNP) array, and whole-exome sequencing (WES) were conducted to determine the genetic etiology of patients. RESULTS: A total of 35 patients with POI were first evaluated by karyotype analysis, and chromosomal anomaly was detected in three (8.5%) and FMR1 premutation was detected in six patients (17%) from two different families. A total of 29 patients without FMR1 premutation were included in the SNP array analysis, and one patient had a 337-kb deletion in the chromosome 6q26 region including PARK2 gene, which was thought to be associated with POI. Twenty-nine cases included in SNP array analysis were evaluated simultaneously with WES analysis, and genetic variant was detected in 55.1% (16/29). CONCLUSION: In the present study, rare novel variants were identified in genes known to be associated with POI, which contribute to the mutation spectrum. The effects of detected novel genes and variations on different pathways such as gonadal development, meiosis and DNA repair, or metabolism need to be investigated by experimental studies. Molecular etiology allows accurate genetic counseling to the patient and family as well as fertility planning.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

OBJECTIVE: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. METHODS: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. RESULTS: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. CONCLUSION: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.

Individual and Combined Anatomic Risk Factors for the Development of an Anterior Cruciate Ligament Rupture in Men: A Multiple Factor Analysis Case-Control Study.

BACKGROUND: No comparative studies have evaluated anatomic risk factors in a large cohort including both patients with anterior cruciate ligament (ACL) ruptures and healthy participants. PURPOSE: To determine which anatomic parameters are independently associated with an ACL rupture and the diagnostic values of the individual and combined anatomic parameters. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 352 male patients who underwent arthroscopic ACL reconstruction because of a primary ACL rupture and 350 age-, sex-, body mass index-, and side dominance-matched healthy participants were included. Measurements of 32 previously determined parameters and 7 calculations were performed. Between-group differences were calculated. Univariate and multivariate logistic regression models and receiver operating characteristic curve analysis were conducted for the individual and combined independently associated factors. RESULTS: The mean age and body mass index of all participants were 29.9 ± 7.7 years and 27.2 ± 3.1, respectively. There were significant differences between the groups regarding the notch width (NW), notch shape index, anterior tibial slope, notch width index, NW-eminence width (NW:EW) ratio, notch height, axial lateral wall angle, medial intercondylar ridge thickness, alpha angle, medial tibial depth (MTD), lateral tibial slope (LTS), coronal tibial plateau width, eminence width index, tibial proximal anteroposterior distance (TPAP), lateral condylar anteroposterior distance (LCAP)/TPAP, ACL cross-sectional area, ACL volume, medial and lateral meniscal cartilage height, medial and lateral meniscal cartilage angle (MCA), and medial and lateral meniscal cartilage bone height. The NW:EW ratio (odds ratio [OR], 4.419; P = .017), MTD (OR, 8.617; P = .001), LTS (OR, 2.254; P = .011), LCAP/TPAP (OR, 2.782; P = .037), and medial MCA (OR, 1.318; P = .010) were independently associated with the development of an ACL rupture. Combining the independently associated factors revealed a sensitivity of 93% and a specificity of 94% (area under the curve, 0.968). CONCLUSION: Patients with ACL ruptures could be distinguished from uninjured controls with high sensitivity and specificity via the combined use of the NW:EW ratio, MTD, LTS, LCAP/TPAP, and medial MCA. In clinical practice, these findings may contribute to the development of preventive strategies for ACL ruptures.

Does Treatment with Dexmedetomidine Intra-articularly Improve Postoperative Pain and Rehabilitation after Anterior Cruciate Ligament Reconstruction?

This study aims to evaluate the analgesic efficacy of dexmedetomidine added to levobupivacaine following anterior cruciate ligament (ACL) surgery. Fifty patients undergoing ACL reconstruction were included. Group DL (dexmedetomidin-levobupivacaine) received 20 mL 0.5% levobupivacaine plus 1 mL (100 µg) dexmedetomidine. Group L (levobupivacaine) patients received 20 mL 0.5% levobupivacaine plus 1 mL saline 10 minutes before tourniquet release. A patient-controlled analgesia (PCA) pump was then connected, delivering 0.5 mg at every 10 minutes and 1-mg morphine and 75-mg diclofenac sodium was used as a rescue analgesic. Postoperative pain was evaluated 0, 2, 4, 6, 12, and 24 hours after extubation at rest and during movement. A rehabilitation program was started after surgery. Postoperative continuous passive motion (CPM) starting time, postoperative leg flexion angle, and straight leg lifting time were evaluated for each group. There were no significant differences between the groups in terms of demographic data and operation time. Morphine consumption, analgesic requirements, and visual analogue scale (VAS) assessments were significantly lower in group DL during the 24-hour period after surgery. The time to start CPM in the postoperative period was significantly shorter in group DL. Passive joint flexion angle was significantly higher in group DL. Postoperative straight leg lifting time was significantly shorter in group DL. Adding dexmedetomidine to the intra-articular levobupivacaine provided better postoperative pain control and improved rehabilitation period after ACL surgery.

The impact of the level of anxiety and temperament in asymptomatic or mildly symptomatic patients requesting implant removal surgery after tibia intramedullary nailing.

BACKROUND: Implant removal (IR) surgery is one of the most frequent procedures in orthopedic practice. Many of the IR surgeries result from patient request rather than a medical necessity. The purpose of the study was to investigate the association between the level of anxiety, type of temperament and psychopathological status, and the willingness to receive IR surgery in asymptomatic or mildly symptomatic patients. We also aimed to compare pre- and postoperative pain scores and document the complication rates after IR surgery. METHODS: The patients who received tibia intramedullary nailing after tibia diaphyseal fracture with a minimum of 18 months follow-up were included in the study. A total of 246 asymptomatic or mildly symptomatic patients were evaluated, and all patients received detailed oral and written information about the risks of IR surgery. The patients who wished to receive IR surgery were called Group 1 (N = 104), and the patients who did not wish to have surgery were called Group 2 (N = 146). All patients were referred to a psychologist to complete the Beck anxiety inventory (BAI), Symptom checklist-90-R (SCL-R-90), and the Temperament Evaluation of Memphis, Pisa, and San Diego Autoquestionnaire (TEMPS-A). RESULTS: The mean age of the patients was 32.31 ± 9.56. One hundred thirteen (45.9%) of the patients were male, and 133 were female (54%). Mean BAI and SCL-90-R were higher in Group 1 than Group 2 (P = 0.001). Anxious and irritable temperament was higher in Group 1 (P = 0.045 and P = 0.035 respectively), and non-dominant and hyperthymic temperament was higher in Group 2 (P = 0.02 and P = 0.04 respectively). CONCLUSIONS: The level of anxiety and type of temperament is associated with the willingness to receive implant removal surgery in asymptomatic or mildly symptomatic patients. Measures to reduce anxiety levels may reduce the rate of unnecessary implant removal surgeries, associated patient care costs, and potential complications.

Comparison of Arthroscopic Treatment Methods in Talar Osteochondral Lesions: A Multicenter, Prospective, Randomized Clinical Trial.

BACKGROUND: The aim of the present study was to contribute new and updated information to the literature by comparing the clinical and radiologic results of arthroscopic microfracture, platelet-rich plasma (PRP) after arthroscopic microfracture, and BST-Cargel scaffold application after arthroscopic microfracture in the treatment of talar osteochondral lesions. METHODS: Sixty-two talar osteochondral lesion patients (31 women and 31 men) who underwent ankle arthroscopy in two different centers were randomized into three groups. The first group consisted of patients who underwent only arthroscopic microfracture (MF) (n = 22); the second group consisted of patients who underwent the PRP procedure after arthroscopic MF (PRP; n = 19); and the third group consisted of patients who underwent the BST-Cargel procedure after arthroscopic MF was (BST-Cargel; n = 21). The talar osteochondral lesions in the three groups were classified according to magnetic resonance and arthroscopic images. American Orthopedic Foot and Ankle Society, Foot and Ankle Ability Measurement (overall pain, 15-minute walking, running function), and visual analog scale scores were evaluated preoperatively and postoperatively, and postoperative return time to sports activities was performed. RESULTS: Compared to the preoperative score, postoperative American Orthopedic Foot and Ankle Society score increased 48.80 ± 9.60 in the BST-Cargel group, whereas there was an increase of 46.68 ± 3.65 in the PRP group and 29.63 ± 3.69 in the MF group, which were statistically significant (P < .05).There was a statistically significant postoperative change in the visual analog scale scores of the patients in all three groups compared to the preoperative scores (P < .05). At the end of the follow-up, the Foot and Ankle Ability Measurement overall pain, 15-minute walking, and running function results of all three groups increased significantly postoperatively compared to the preoperative values (P < .005). CONCLUSIONS: BST-Cargel application with microfracture is a method that can be applied easily and safely with arthroscopy to lesions larger than 1.5 cm2 regardless of the size of the cartilage defect, and it has been found to be superior to the other two methods in terms of pain, functional score, radiologic recovery, and return to sports activities.

Genetic and Clinical Characterization of Patients with Maturity-Onset of Diabetes of the Young (MODY): Identification of Novel Variations.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is a rare monogenic type of diabetes, and accounts for 2-5% of all diabetes cases. An early age of onset, a family history supporting autosomaldominant inheritance, insulin resistance, and the absence of autoimmunity are the major characteristics of MODY. However, genetic testing is crucial for diagnosis. AIMS: To investigate the 7 MODY-related genes and clinical findings of patients with a preliminary clinical diagnosis of MODY. STUDY DESIGN: Retrospective cross-sectional study. METHODS: In this study, 7 genes (KCNJ11, ABCC8, INS, GCK, HNF4A, HNF1A, and HNF1B) related to MODY were screened via targeted sequencing in 182 cases with a confirmed pre-diagnosis of MODY. The clinical characteristics of the patients were evaluated retrospectively. RESULTS: A total of 182 patients, 48% of whom were women, between the ages of 18-62 were included in the study. In 30 cases (16.4%), 28 different pathogenic variations were found, of which 20 were previously reported and 8 were novel variations segregated by disease within the family. Pathogenic variations were detected in the following genes in order of mutation frequency; GCK, HNF1A, ABCC8, HNF4A, HNF1B and KCNJ11. Interestingly, six of the 30 cases (20%) carried a pathogenic variation in the ABCC8 gene. No mutation was detected in the INS gene. A family history of vertically transmitted diabetes and elevated HbA1C at the time of diagnosis were found in 20 (66%) and 16 (52%) cases, respectively. CONCLUSION: In this series, 28 different pathogenic variations are identified, 8 of which are novel. The rate of pathogenic variation in the ABCC8 gene is unexpectedly high. Two-thirds of cases have a family history of vertically transmitted diabetes.