Evaluation of Blood Culture Results in Patients with Malignancy in Erzurum Province, Turkey.

Background: Bloodstream infections are a serious public health problem that requires follow-up with blood culture; this negatively affects the course of the disease and patient healthcare costs in patients with malignancy. This study aimed to determine the growth frequency of pathogens and their antibiotic resistance profiles in the blood cultures of patients with hematological and oncogenic malignancies. Materials and methods: The results of 7451 blood cultures, obtained from 2926 patients between January 2017 and January 2022, were evaluated retrospectively. Of these cultures, 3969 were obtained from patients with malignancy (diagnostic codes C00-D48 in ICD-10) and 3482 from patients without malignancy. The hospital information management system modules were used to acquire patient data and blood culture results. Results: Various microorganisms grew in 10.1% of blood cultures. Of these organisms, 64.1% were isolated from cases of malignancy. Of the pathogens, 49.2% were gram-negative bacteria, 47.7% were gram-positive bacteria, and 3.1% were fungi. The most frequently isolated bacteria were methicillin-resistant coagulase-negative staphylococci (3.2%), Escherichia coli (2.3%), Klebsiella pneumoniae (1.0%), methicillin-sensitive coagulase-negative staphylococci (0.7%), and Staphylococcus aureus (0.6%). Pathogen positivity was highest in the patient cultures with urinary system cancer (23.9%), thyroid and other endocrine gland cancers (20.6%), female and male genital organ cancers (18.2%/16.9%), and digestive organ cancer (14.2%). Gram-negative bacteria to ampicillin, piperacillin, and sulfamethoxazole-trimethoprim and Gram-positive bacteria to penicillin, erythromycin, and sulfamethoxazole-trimethoprim were highly resistant. Combined resistance to imipenem and meropenem was observed in 25 Gram-negative bacteria. Twelve (48%) of the carbapenem-resistant bacteria were isolated from patients with lymphoid, hematopoietic, and related tissue malignant neoplasia. Conclusion: This study reported microorganisms and their antimicrobial resistance in the blood cultures of malignant patients, a special patient group. It pointed out that the antibiotic resistance of Staphylococcus, Klebsiella pneumoniae, and E. coli is high enough to cause problems in the treatment of patients with malignancy.

False-Negative PET/CT scan with Metastatic Sebaceous Carcinoma: An Important Diagnostic Consideration.

Positron emission tomography (PET) has gained widespread acceptance as a valuable diagnostic tool for cancer. It is rare for a PET/CT scan to overlook the presence of metastatic disease. Sebaceous carcinoma is an uncommon malignant tumour that typically originates in the skin of the eyelid. In this case report, we present a unique case involving a metastatic sebaceous carcinoma that was not initially detected by a PET/CT scan in an 88-year-old female. Therefore, clinicians must maintain a heightened awareness of sebaceous carcinoma and exercise caution when making decisions solely based on PET scan results. It is crucial to recognise this potential limitation of PET scans in sebaceous carcinoma and consider further diagnostic approaches to ensure timely and accurate detection of sebaceous carcinoma. LEARNING POINTS: PET scans may miss slow-growing tumours such as sebaceous carcinoma.A high index of suspicion for sebaceous carcinoma is crucial, even with negative PET scans. Additional diagnostic approaches might be necessary for accurate detection.Sebaceous carcinoma is a rare but aggressive cancer. Diagnosis can be challenging due to its varied presentations.

Risk Factors for Residual Back Pain After Balloon Kyphoplasty for Osteoporotic Vertebral Fracture.

Background: Balloon kyphoplasty (BKP) is a method for the management of osteoporotic vertebral body fracture (OVF). However, improvement in back pain (BP) is poor in some patients, also previous reports have not elucidated the exact incidence and risk factors for residual BP after BKP. We clarified the characteristics of residual BP after BKP in patients with OVF. Hypothesis: In this study, we hypothesize that some risk factors may exist for residual BP 2 years after the treatment of OVF with BKP. Patients and Methods: A multicenter cohort study was performed where patients who received BKP within 2 months of OVF injury were followed-up for 2 years. BP at 6 months after surgery and final observation was evaluated by Visual Analog Scale (VAS) score. Patients with a score of 40 mm or more were allocated to the residual BP group, and comparisons between the residual back pain group and the improved group were made for bone density, kyphosis, mobility of the fractured vertebral body, total spinal column alignment, and fracture type (fracture of the posterior element, pedicle fracture, presence or absence of posterior wall damage, etc.). Also, Short Form 36 (SF-36) for physical component summary (PCS) and mental component summary (MCS) at the final follow-up was evaluated in each radiological finding. Results: Of 116 cases, 79 (68%) were followed-up for 2 years. Two years after the BKP, 26 patients (33%) experienced residual BP. Neither age nor sex differed between the groups. In addition, there was no difference in bone mineral density, BKP intervention period (period from onset to BKP), and osteoporosis drug use. However, the preoperative height ratio of the vertebral body was significantly worse in the residual BP group (39.8% vs. 52.1%; p = 0.007). Two years after the operation, the vertebral body wedge angle was significantly greater in the residual BP group (15.7° vs. 11.9°; p = 0.042). In the multiple logistic regression model with a preoperative vertebral body height ratio of 50% or less [calculated by receiver operating characteristic (ROC) curve], the adjusted odds ratio for residual BP was 6.58 (95% confidence interval 1.64-26.30; p = 0.007); similarly, patients with vertebral body height ratio less than 50% had a lower score of SF-36 PCS 24.6 vs. 32.2 p = 0.08. Conclusion: The incidence of residual BP 2 years after BKP was 33% in the current study. The risk factor for residual BP after BKP was a preoperative vertebral body height ratio of 50% or less, which should be attentively assessed for the selection of a proper treatment scheme and to provide adequate stabilization. Level of Evidence: III.

Mediastinal Bronchogenic Cyst With Superior Vena Cava Syndrome: A Case Report.

Bronchogenic cysts are rare in adults and often remain undetected until discovered incidentally on imaging or during a symptomatic investigation. The possibility of superior vena cava (SVC) compression due to a bronchogenic cyst arises in complex patient presentations. SVC syndrome poses several unique challenges due to the wide range of clinical symptoms and difficulty identifying the cause when symptoms first manifest. This case report examines a 39-year-old male who presented with symptoms resulting from SVC compression caused by a bronchogenic cyst, leading to SVC syndrome. We discuss the various imaging modalities used to assess the severity of the obstruction and the surgical interventions employed to alleviate the symptoms. A surgical intervention provides symptomatic relief and promises an excellent prognosis when performed without complications.

Factors Affecting Smoking Cessation After Acute Myocardial Infarction.

OBJECTIVE: Persistent smoking after acute myocardial infarction is associated with an increased risk of recurrent cardiovascular events. Our aim was to determine the changes in smoking habits in patients after acute myocardial infarction and evaluate the factors affecting smoking cessation. MATERIAL AND METHODS: A total of 322 patients who had an acute myocardial infarction while smoking were included in the study. Participants were asked to fill out a 30-question survey. According to smoking status, 2 groups were identified, those who quit smoking (n = 155) and those who continued smoking (n = 167). RESULTS: The rate of smoking cessation among study participants was 48.2% (n = 155). Most of smoker participants had the intention to quit smoking (n = 124, 74.2%). The most common barriers for smoking cessation were nicotine withdrawal symptoms and the cessation rate was over 3 times higher in those with low nicotine dependence (P < .01). Weight gain was another common problem seen in 163 (50.6%) participants; among which the cessation rate was relatively low (43.6%). A total of 231 (71.7%) participants got an advice from their doctor to quit smoking and the probability of quitting was around 5 times higher in this group (P < .01). A total of 174 (54%) participants stated that they were considering quitting whenever they see the pictorial health warnings on cigarette packs and the probability of quitting was doubled in this group (P < .01). CONCLUSION: High number of patients continue on smoking after acute myocardial infarction. The most common barriers for smoking cessation are nicotine withdrawal symptoms. Doctors should play an active role in helping the patient quit smoking. Strict regulations of tobacco control can be very helpful in this regard.

Twelve years of experience in the treatment of newborns with intrauterine gastrointestinal perforation.

BACKGROUND: Meconium peritonitis occurs when meconium leaks into the peritoneal cavity as a result of intrauterine gastrointestinal perforation. In this study, we aimed to evaluate the results of newborn patients who were followed and treated due to intrauterine gastrointestinal perforation in the pediatric surgery clinic. METHODS: All newborn patients who were followed up and treated for intrauterine gastrointestinal perforation in our clinic between December 2009-2021 were analyzed retrospectively. Newborns who had no congenital gastrointestinal perforation were not included in our study. The data were analyzed using NCSS (Number Cruncher Statistical System) 2020 Statistical Software. RESULTS: Within twelve years, intrauterine gastrointestinal perforation was detected in 41 newborns, including 26 (63.4%) males, and 15 (36.6%) patients who were operated on in our pediatric surgery clinic. Surgical findings of 41 patients diagnosed with intrauterine gastrointestinal perforation revealed the presence of volvulus (n=21), meconium pseudocyst (n=18), jejunoileal atresia (n=17), malrotation-malfixation anomaly (n=6), volvulus due to internal hernia (n=6), Meckel`s diverticulum (n=2), gastroschisis (n=2), perforated appendicitis (n=1), anal atresia (n=1), and gastric perforation (n=1). Eleven patients (26.8%) died. Total intubation time was significantly higher in deceased cases. Postoperatively, deceased cases passed their first stool significantly earlier than surviving newborns. Besides, ileal perforation was seen significantly more frequently in deceased cases. However, the frequency of jejunoileal atresia was significantly lower in the deceased patients. CONCLUSIONS: Although sepsis has been held primarily responsible for the deaths in these infants from past to present, insufficiency in lung capacity necessitating intubation negatively affects their survival. Early passage of stool is not always an indicator of good prognosis after the operation, and patients may die due to malnutrition and dehydration, even after they are discharged after feeding, defecating and having weight gain.

Protocol for management of pregnant patients requiring emergency minor oral surgical procedures: a prospective study in 52 patients.

Objectives: Dental or maxillofacial emergencies are uncommon during pregnancy, but if they occur, they are challenging to treat due to potential risks. The mother should not be denied necessary medical or dental care because of pregnancy. The aim of the study is to observe outcomes of pregnancy in patients requiring emergency minor oral surgical procedures during gestation and to determine the safety of the pregnant woman undergoing the procedure and the fetus. Materials and Methods: The study was conducted on 52 pregnant women requiring emergency oral surgical procedures. A standard treatment protocol for treatment of specific entities was followed. Close monitoring and observation were the primary goal of treatment. All patients were followed postoperatively until complete recovery from the surgical procedures and then until birth of the baby. A control group of 52 healthy pregnant patients who did not require oral surgical procedures was considered for statistical analysis. The measurements to calculate observation were fetal loss (spontaneous abortion), preterm birth, low-birth weight, or incidence of any congenital anomalies in the baby and its association with surgical procedures. Results: No fetal loss occurred in any of the cases. However, four patients experienced preterm birth and seven neonates exhibited low birth weights. No congenital abnormalities were discovered. In one instance, a patient who underwent surgery for a mandibular symphysis fracture under general anesthesia in the 31st week of pregnancy experienced labor pain on the fourth postoperative day, requiring an emergency Caesarean section. Conclusion: The results of our study demonstrate that, compared to the control group, minor emergency surgeries performed during pregnancy have no discernible negative effects on the fetus. These procedures can safely be performed by adhering to our described protocols.

Tobacco harm reduction in Afghanistan: a recipe for improving smokers' health.

Tobacco Harm Reduction (THR) offers a promising approach to addressing the significant burden of smoking in Afghanistan. Over three million Afghans smoke daily, making it a leading cause of preventable deaths in the country. While the previous Afghan government implemented various tobacco cessation policies and strategies, these measures were only partially effective in reducing the number of smokers or smoking-related deaths. In 2021, community-based initiatives in Kabul and Herat started advocating for Tobacco Harm Reduction (THR) as a novel, realistic, and practical approach proven to promote smoking abstinence and minimize tobacco harm. However, implementing THR strategies in Afghanistan faces numerous challenges, including a lack of governmental support, funding issues, unfavorable market conditions, the high cost-effectiveness of THR products, and misconceptions about these products. To effectively promote THR in Afghanistan and overcome these challenges, it will be necessary to implement THR policies that support THR products for smokers, regulate the market for these products, produce them locally with healthcare professional oversight, conduct more engaging advocacy campaigns, and secure domestic sponsors.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Advances in Artificial Intelligence to Diagnose Otitis Media: State of the Art Review.

OBJECTIVE: Otitis media (OM) is a model disease for developing, validating, and implementing artificial intelligence (AI) techniques. We aim to review the state of the art applications of AI used to diagnose OM in pediatric and adult populations. DATA SOURCES: Several comprehensive databases were searched to identify all articles that applied AI technologies to diagnose OM. REVIEW METHODS: Relevant articles from January 2010 through May 2021 were identified by title and abstract. Articles were excluded if they did not discuss AI in conjunction with diagnosing OM. References of included studies and relevant review articles were cross-referenced to identify any additional studies. CONCLUSION: Title and abstract screening resulted in full-text retrieval of 40 articles that met initial screening parameters. Of this total, secondary review articles (n = 7) and commentary-based articles (n = 2) were removed, as were articles that did not specifically discuss AI and OM diagnosis (n = 5), leaving 25 articles for review. Applications of AI technologies specific to diagnosing OM included machine learning and natural language processing (n = 23) and prototype approaches (n = 2). IMPLICATIONS FOR PRACTICE: This review emphasizes the utility of AI techniques to automate and aid in diagnosing OM. Although these techniques are still in the development and testing stages, AI has the potential to improve the practice of otolaryngologists and primary care clinicians by increasing the efficiency and accuracy of diagnoses.

Phylogeography of cliff racer (Platyceps rhodorachis Jan, 1865) from Punjab, Pakistan / Filografia de penhasco (Platyceps rhodorachis Jan, 1865) de Punjab, Paquistão

The present study reports the existence of cliff racer, Platyceps rhodorachis from the plains of Punjab, Pakistan. A total of 10 specimens were captured during the field surveys from June to September, 2018 from different sites of Punjab. Platyceps rhodorachis was identify on the basis of morphology and confirmed through COI gene sequences. The obtained DNA sequences have shown reliable and exact species identification. Newly produced DNA sequences of Platyceps rhodorachis were submitted to GenBank and accession numbers were obtained (MK936174.1, MK941839.1 and MT790210.1). N-J tree based on COI sequences of Platyceps rhodorachis clearly separated as out-group with other members of family Colubridae based on p-distance. The intra-specific genetic variation ranges from 12% to 18%. The DNA sequences of Platyceps rhodorachis kashmirensis, Platyceps rhodorachis ladacensis, Platyceps ventromaculatus, Platyceps ventromaculatus bengalensis and Platyceps ventromaculatus indusai are not available at NCBI to validate their taxonomic positions. In our recommendations, a large scale molecular based identification of Pakistan’s herpetofauna is required to report more new or subspecies from country.

O presente estudo relata a existência de um corredor de penhasco, Platyceps rhodorachis, das planícies de Punjab, Paquistão. Um total de 10 espécimes foi capturado durante os levantamentos de campo de junho a setembro de 2018 em diferentes locais de Punjab. Platyceps rhodorachis foi identificada com base na morfologia e confirmada por meio de sequências do gene COI. As sequências de DNA obtidas mostraram identificação de espécies confiável e exata. Sequências de DNA de Platyceps rhodorachis recém-produzidas foram submetidas ao GenBank e os números de acesso foram obtidos (MK936174.1, MK941839.1 e MT790210.1). Árvore N-J baseada em sequências COI de Platyceps rhodorachis claramente separadas como out-group com outros membros da família Colubridae com base na distância-p. A variação genética intraespecífica varia de 12% a 18%. As sequências de DNA de Platyceps rhodorachis kashmirensis, Platyceps rhodorachis ladacensis, Platyceps ventromaculatus, Platyceps ventromaculatus bengalensis e Platyceps ventromaculatus indusai não estão disponíveis no NCBI para validar suas posições taxonômicas. Em nossas recomendações, uma identificação de base molecular em grande escala da herpetofauna do Paquistão é necessária para relatar mais novas ou subespécies do país.

Phylogeography of cliff racer (Platyceps rhodorachis Jan, 1865) from Punjab, Pakistan

Abstract The present study reports the existence of cliff racer, Platyceps rhodorachis from the plains of Punjab, Pakistan. A total of 10 specimens were captured during the field surveys from June to September, 2018 from different sites of Punjab. Platyceps rhodorachis was identify on the basis of morphology and confirmed through COI gene sequences. The obtained DNA sequences have shown reliable and exact species identification. Newly produced DNA sequences of Platyceps rhodorachis were submitted to GenBank and accession numbers were obtained (MK936174.1, MK941839.1 and MT790210.1). N-J tree based on COI sequences of Platyceps rhodorachis clearly separated as out-group with other members of family Colubridae based on p-distance. The intra-specific genetic variation ranges from 12% to 18%. The DNA sequences of Platyceps rhodorachis kashmirensis, Platyceps rhodorachis ladacensis, Platyceps ventromaculatus, Platyceps ventromaculatus bengalensis and Platyceps ventromaculatus indusai are not available at NCBI to validate their taxonomic positions. In our recommendations, a large scale molecular based identification of Pakistans herpetofauna is required to report more new or subspecies from country.

Resumo O presente estudo relata a existência de um corredor de penhasco, Platyceps rhodorachis, das planícies de Punjab, Paquistão. Um total de 10 espécimes foi capturado durante os levantamentos de campo de junho a setembro de 2018 em diferentes locais de Punjab. Platyceps rhodorachis foi identificada com base na morfologia e confirmada por meio de sequências do gene COI. As sequências de DNA obtidas mostraram identificação de espécies confiável e exata. Sequências de DNA de Platyceps rhodorachis recém-produzidas foram submetidas ao GenBank e os números de acesso foram obtidos (MK936174.1, MK941839.1 e MT790210.1). Árvore N-J baseada em sequências COI de Platyceps rhodorachis claramente separadas como out-group com outros membros da família Colubridae com base na distância-p. A variação genética intraespecífica varia de 12% a 18%. As sequências de DNA de Platyceps rhodorachis kashmirensis, Platyceps rhodorachis ladacensis, Platyceps ventromaculatus, Platyceps ventromaculatus bengalensis e Platyceps ventromaculatus indusai não estão disponíveis no NCBI para validar suas posições taxonômicas. Em nossas recomendações, uma identificação de base molecular em grande escala da herpetofauna do Paquistão é necessária para relatar mais novas ou subespécies do país.

EPAC Regulates Melanoma Growth by Stimulating mTORC1 Signaling and Loss of EPAC Signaling Dependence Correlates with Melanoma Progression.

Exchange proteins directly activated by cAMP (EPAC) belong to a family of RAP guanine nucleotide exchange factors (RAPGEF). EPAC1/2 (RAPGEF3/4) activates RAP1 and the alternative cAMP signaling pathway. We previously showed that the differential growth response of primary and metastatic melanoma cells to cAMP is mediated by EPAC. However, the mechanisms responsible for this differential response to EPAC signaling are not understood. In this study, we show that pharmacologic inhibition or siRNA-mediated knockdown of EPAC selectively inhibits the growth and survival of primary melanoma cells by downregulation of cell-cycle proteins and inhibiting the cell-cycle progression independent of ERK1/2 phosphorylation. EPAC inhibition results in upregulation of AKT phosphorylation but a downregulation of mTORC1 activity and its downstream effectors. We also show that EPAC regulates both glycolysis and oxidative phosphorylation, and production of mitochondrial reactive oxygen species, preferentially in primary melanoma cells. Employing a series of genetically matched primary and lymph node metastatic (LNM) melanoma cells, and distant organ metastatic melanoma cells, we show that the LNM and metastatic melanoma cells become progressively less responsive and refractory to EPAC inhibition suggesting loss of dependency on EPAC signaling correlates with melanoma progression. Analysis of The Cancer Genome Atlas dataset showed that lower RAPGEF3, RAPGEF4 mRNA expression in primary tumor is a predictor of better disease-free survival of patients diagnosed with primary melanoma suggesting that EPAC signaling facilitates tumor progression and EPAC is a useful prognostic marker. These data highlight EPAC signaling as a potential target for prevention of melanoma progression. IMPLICATIONS: This study establishes loss of dependency on EPAC-mTORC1 signaling as hallmark of primary melanoma evolution and targeting this escape mechanism is a promising strategy for metastatic melanoma.

Incidence of postoperative progressive segment degeneration at decompression and adjacent segments after minimally invasive lumbar decompression surgery: a 5-year follow-up study.

OBJECTIVE: There are several reported studies on the incidence of adjacent segment disease (ASD) after lumbar fusion surgery; however, the incidence of ASD after decompression surgery has not been well studied. In this study the authors aimed to investigate the incidence of progressive segment degeneration (PSD) at the decompression and adjacent segments 5 years after minimally invasive lumbar decompression surgery. METHODS: We investigated data from 168 patients (mean age, 69.5 ± 9.2 years) who underwent bilateral microscopic or microendoscopic decompression surgery via a unilateral approach and were followed up for more than 5 years. Outcomes were self-reported visual analog scale (VAS) scores for low-back pain, leg pain, and leg numbness and physician-assessed Japanese Orthopaedic Association (JOA) scores for back pain. Changes in the disc height and movement of the adjacent lumbar segments were compared using preoperative and 5-year postoperative lateral full-length standing whole-spine radiographic images. PSD was defined as loss of disc height > 3 mm and progression of anterior or posterior slippage > 3 mm. The incidence and clinical impact of PSD were investigated. RESULTS: The mean JOA score improved significantly in all patients from 13.4 points before surgery to 24.1 points at the latest follow-up (mean recovery rate 67.8%). PSD at the decompression site was observed in 43.5% (73/168) of the patients. The proportions of patients with loss of disc height > 3 mm and slippage progression were 16.1% (27/168) and 36.9%, respectively (62/168: 41 anterior and 21 posterior). The proportion of patients with PSD at the adjacent segment was 20.5% (35/168), with 5.4% (9/168) of the patients with loss of disc height > 3 mm and 16.0% (27/168: 13 anterior and 14 posterior) with slippage progression. There was no significant difference in the clinical outcomes between patients with and those without PSD. CONCLUSIONS: Radiological ASD was observed even in the case of decompression surgery alone. However, there was no correlation with symptom deterioration, measured by the VAS and JOA scores.

Mid-term changes in spinopelvic sagittal alignment in lumbar spinal stenosis with coexisting degenerative spondylolisthesis or scoliosis after minimally invasive lumbar decompression surgery: minimum five-year follow-up.

BACKGROUND CONTEXT: Recently, the number of patients with lumbar spinal stenosis (LSS) who present with a coexisting spinal deformity such as degenerative spondylolisthesis (DS) and scoliosis (DLS) has been increasing. Lumbar decompression without fusion can lead to a reactive improvement in the lumbar and sagittal spinopelvic alignment, even if a sagittal imbalance exists preoperatively. However, the mid- to long-term impact of the coexistence of DS and DLS on the change in sagittal spinopelvic alignment and clinical outcomes after decompression surgery remains unknown. PURPOSE: This study aimed to investigate whether the coexistence of DS or DLS in patients with LSS is associated with differences in radiological and clinical outcomes after minimally invasive lumbar decompression surgery. STUDY DESIGN/SETTING: A retrospective analysis of prospectively collected data. PATIENT SAMPLE: A total of 169 patients who underwent minimally invasive lumbar decompression surgery and follow-up >5 years postoperatively. OUTCOME MEASURES: Self-report measures: Low back pain (LBP) and/or leg pain and/or leg numbness visual analog scale (VAS) scores and the Japanese Orthopedic Association scores. PHYSIOLOGIC MEASURES: Standing sagittal spinopelvic alignment. METHODS: In total, 81 patients with LSS, 50 patients with LSS and DS (≥3 mm anterior slippage), and 38 patients with LSS and DLS (≥15° coronal Cobb angle) were included in the current study. Clinical and radiological outcome results before surgery and at 2 and 5 years after surgery were compared among the groups. RESULTS: In patients with LSS with coexisting DS, the clinical outcomes at 2, and 5 years after surgery were similar to those of patients with only LSS. In patients with LSS with coexisting DLS, the VAS LBP and leg pain at 2 years after surgery was significantly higher (34.7 vs. 27.8, p=0.014; 27.8 vs. 14.7, p=0.028) and the achievement rate of the minimal clinically important difference in VAS LBP and leg pain was significantly lower than that of the LSS group (36.1% vs. 54.2%, p=0.036; 58.3% vs. 69.9%, p=0.10). The clinical outcomes except VAS leg numbness at 5 years after surgery were similar to those of patients with only LSS. The reoperation rate of the DS group was significantly lower than that of the LSS group (4.0% vs. 14.8%; p=0.01); however, the reoperation rate of the DLS group was comparable to that of the LSS group (15.8% vs. 14.8%; p=0.493). Lumbar lordosis (LL), sacral slope, pelvic tilt, and pelvic incidence-LL had significantly improved and been maintained for 5 years after the surgery in both the DS and the DLS groups. The sagittal vertical axis had improved at two-year follow-up; however, no significant difference was observed at the 5-year follow-up in both the DS, and the DLS groups. CONCLUSIONS: Mid-term clinical outcomes in patients with LSS with and without deformity were comparable. Lumbar decompression without fusion can result in a reactive improvement in the lumbar and sagittal spinopelvic alignment, even with coexisting DS or DLS. Minimally invasive surgery could be considered for most patients with LSS.

Expression and function of fibroblast growth factor 1 in the hypertrophied ligamentum flavum of lumbar spinal stenosis.

BACKGROUND: Fibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures. METHODS: We obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-ß1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-ß1-induced myofibroblast differentiation and fibrosis. RESULTS: Immunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-ß1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-ß1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells. CONCLUSION: FGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-ß1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy.

Design, synthesis and broad spectrum antibreast cancer activity of diarylindoles via induction of apoptosis in aggressive breast cancer cells.

Breast cancer is the second leading cause of cancer deaths in women with significant morbidity and mortality. Present study describes design, synthesis and detailed pharmacology of indole derivatives exhibiting remarkable broad spectrum antiproliferative activity against breast cancer cells. Detailed mechanistic evaluations confirmed induction of G0/G1 arrest, apoptosis induction, loss of mitochondrial integrity, enhanced ROS generation, autophagy, estrogen receptor ß-transactivation and increased tubulin polymerization. In in-vivo efficacy studies in rodent model, these indole derivatives induced significant regression in mice mammary tumour on 21 days daily oral dose. Moreover, compounds 19 and 23 were safe in Swiss albino mice in safety studies. These diarylindoles may further be optimized for better efficacy.

The effect of minimally invasive lumbar decompression surgery on sagittal spinopelvic alignment in patients with lumbar spinal stenosis: a 5-year follow-up study.

OBJECTIVE: Several studies have examined the relationship between sagittal spinopelvic alignment and clinical outcomes after spinal surgery. However, the long-term reciprocal changes in sagittal spinopelvic alignment in patients with lumbar spinal stenosis after decompression surgery remain unclear. The aim of this study was to investigate radiographic changes in sagittal spinopelvic alignment and clinical outcomes at the 2-year and 5-year follow-ups after minimally invasive lumbar decompression surgery. METHODS: The authors retrospectively studied the medical records of 110 patients who underwent bilateral decompression via a unilateral approach for lumbar spinal stenosis. Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) scores for low-back pain (LBP), leg pain, leg numbness, and spinopelvic parameters were evaluated before surgery and at the 2-year and 5-year follow-ups. Sagittal malalignment was defined as a sagittal vertical axis (SVA) ≥ 50 mm. RESULTS: Compared with baseline, lumbar lordosis significantly increased after decompression surgery at the 2-year (30.2° vs 38.5°, respectively; p < 0.001) and 5-year (30.2° vs 35.7°, respectively; p < 0.001) follow-ups. SVA significantly decreased at the 2-year follow-up compared with baseline (36.1 mm vs 51.5 mm, respectively; p < 0.001). However, there was no difference in SVA at the 5-year follow-up compared with baseline (50.6 mm vs 51.5 mm, respectively; p = 0.812). At the 5-year follow-up, 82.5% of patients with preoperative normal alignment maintained normal alignment, whereas 42.6% of patients with preoperative malalignment developed normal alignment. Preoperative sagittal malalignment was associated with the VAS score for LBP at baseline and 2-year and 5-year follow-ups and the JOA score at the 5-year follow-up. Postoperative sagittal malalignment was associated with the VAS score for LBP at the 2-year and 5-year follow-ups and the VAS score for leg pain at the 5-year follow-up. There was a trend toward deterioration in clinical outcomes in patients with persistent postural malalignment compared with other patients. CONCLUSIONS: After minimally invasive surgery, spinal sagittal malalignment can convert to normal alignment at both short-term and long-term follow-ups. Sagittal malalignment has a negative impact on the VAS score for LBP and a weakly negative impact on the JOA score after decompression surgery.

Convolutional Neural Network-Based Clinical Predictors of Oral Dysplasia: Class Activation Map Analysis of Deep Learning Results.

Oral cancer/oral squamous cell carcinoma is among the top ten most common cancers globally, with over 500,000 new cases and 350,000 associated deaths every year worldwide. There is a critical need for objective, novel technologies that facilitate early, accurate diagnosis. For this purpose, we have developed a method to classify images as "suspicious" and "normal" by performing transfer learning on Inception-ResNet-V2 and generated automated heat maps to highlight the region of the images most likely to be involved in decision making. We have tested the developed method's feasibility on two independent datasets of clinical photographic images of 30 and 24 patients from the UK and Brazil, respectively. Both 10-fold cross-validation and leave-one-patient-out validation methods were performed to test the system, achieving accuracies of 73.6% (±19%) and 90.9% (±12%), F1-scores of 97.9% and 87.2%, and precision values of 95.4% and 99.3% at recall values of 100.0% and 81.1% on these two respective cohorts. This study presents several novel findings and approaches, namely the development and validation of our methods on two datasets collected in different countries showing that using patches instead of the whole lesion image leads to better performance and analyzing which regions of the images are predictive of the classes using class activation map analysis.