Beyond Hormones: Investigating the Impact of Progesterone Receptor Membrane Component 1 in Lung Adenocarcinoma.

Progesterone Receptor Membrane Component 1 (PGRMC1) is a candidate oncogene with a prominent involvement in the pathogenesis of diverse cancers (ovarian, thyroid, breast, colon, head, and neck). Our study ascertains the ability of PGRMC1 to influence WNT members in the non-small cell lung cancer subtype-lung adenocarcinoma (LUAD) and participates in augmented cell proliferation and migration. Both computational and in vitro experimental analyses were performed in this study. Gene silencing, in vitro assays, gene expression & and protein expression studies were performed to ascertain the role of PGRMC1 in LUAD cells. The computational analysis, PGRMC1 gene level expression was analysed using the microarray gene expression omnibus datasets (GSE27262; GSE18842) to compare LUAD tumours and normal tissues. Concurrently, the gene expression profiling interactive analysis of PGRMC1 and Kaplan-Meier survival analysis revealed a decreasing patient survival rate with an increasing PGRMC1 gene expression in LUAD tumour samples. Interestingly, the experimental gene silencing studies were conducted in vitro (si-PGRMC1 Vs si-Control) to understand the essential role of PGRMC1 in regulating WNT-associated genes (WNT1, WNT5A, and WNT11). Comparative experimental cell migration and spheroid formation assays (si-PGRMC1 Vs si-Control) in vitro showed a strong association between PGRMC1 and LUAD. In vitro expression analysis using real-time PCR and western blot further confirmed the connecting link between PGRMC1 and WNT5A compared to other WNT member genes (WNT1 and WNT11) in LUAD. The computational and experimental analyses agreed with one another.

Epidemiology and Survival of Colorectal Cancer in Lebanon: A Sub-National Retrospective Analysis.

BACKGROUND: Scarce data exist about colorectal cancer (CRC) presentation and outcomes in Lebanon. The aim of this study is to describe the characteristics of Lebanese patients diagnosed with colorectal cancer, particularly the method of detection, age of onset, stage at presentation, treatment modalities, and survival. METHODS: This is a retrospective study of a cohort of patients with CRC, diagnosed between 2005 and 2010, admitted to 6 major university-affiliated medical centers in Lebanon. RESULTS: The total sample consisted of 586 patients (median age: 64 years; M:F ratio: 1.25). The most common presenting symptoms were changes in bowel habits, abdominal pain, and blood per rectum. Only 3% had been diagnosed by screening colonoscopy. Of the patients diagnosed with CRC younger than 50 years of age, 72.5% had a positive family history (P = .07). More than two-thirds of patients had an advanced stage of the disease III and IV at presentation. The Kaplan-Meier-estimated survival rate was 0%, 44.5%, 70.2%, and 78.5% for those with stage IV, III, II, and I, respectively (P = .0001), and did not vary by age nor gender of the patient. There was no differential in survival estimate for patients with stage II and III by number of chemotherapy cycles received. However, there was a significant difference in median survivorship for patients with metastatic stage IV disease; those who received less than or equal to 9 cycles had a median survivorship of 2 years (CI: 1.31-2.68) compared to 4 years (CI: 2.36-5.63) for those who received more than 9 cycles (P = .047). The cox regression showed while controlling for age and gender that patients diagnosed at stage IV had a hazard ratio of 8.81 (3.20-24.22) compared to those who were diagnosed at stage I (P = .047). CONCLUSIONS: Lebanese patients affected by colorectal cancer tend to present with advanced disease stages, leading to poor prognosis and survival.

Arthroscopic treatment of osteochondral knee defects with resorbable biphasic synthetic scaffold: clinical and radiological results and long-term survival analysis.

PURPOSE: The aim of our study is to evaluate the long-term results in patients treated with a fully arthroscopic TruFit system for osteochondral lesions of the femoral condyle, analyzing the clinical and radiological outcomes, survival rate, complications, and correlations. METHODS: The study included all patients treated with the TruFit system with a full-thickness focal lesion of the knee cartilage (grade IV according to the ICRS classification), entirely arthroscopically with a minimum follow-up of five years. All patients were evaluated clinically prior to surgery (T0) and at two consecutive follow-ups (T1 36.4 ± 17.03 months and T2 101.63 ± 19.02 months), using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Hospital for Special Surgery Score (HSS). At the final follow-up, the magnetic resonance imaging (MRI) was evaluated by two orthopaedists using the magnetic resonance observation of cartilage repair tissue (MOCART) score. RESULTS: The sample was formed of 21 patients, of which 14 were males (67%) and 7 females (33%), with a mean age of 51.29 ± 10.70. Of the 21 patients, two underwent prosthetic knee replacement at 24 and 65 months, respectively. At T0, the HSS and the KOOS score were, respectively, 60.71 ± 11.62 and 57.71 ± 6.11. For both clinical values, a significant improvement was noted between T0 and T1 (p < 0.05) and between T0 and T2 (p < 0.05). At the final follow-up, the MOCART value was found to be 45.78 ± 5.27. CONCLUSIONS: The study results highlighted the safety and potential of the arthroscopic TruFit system procedure, which offered a good clinical outcome with stable results at long-term follow-up although we found no correlations between the MRI and clinical results.

Survival of low birthweight neonates in Uganda: analysis of progress between 1995 and 2011.

BACKGROUND: Although low birthweight (LBW) babies represent only 15.5% of global births, it is the leading underlying cause of deaths among newborns in countries where neonatal mortality rates are high. In Uganda, like many other sub-Saharan African countries, the progress of reducing neonatal mortality has been slow and the contribution of low birthweight to neonatal deaths over time is unclear. The aim of this study is to investigate the association between low birthweight and neonatal mortality and to determine the trends of neonatal deaths attributable to low birthweight in Uganda between 1995 and 2011. METHODS: Cross-sectional survey datasets from Uganda Demographic and Health Surveys between 1995 and 2011 were analyzed using binary logistic regression with 95% confidence interval (CI) and Kaplan-Meier survival analysis to examine associations and trends of neonatal mortalities with respect to LBW. A total of 5973 singleton last-born live births with measured birthweights were included in the study. RESULTS: The odds of mortality among low birthweight neonates relative to normal birthweight babies were; in 1995, 6.2 (95% CI 2.3 -17.0), in 2000-2001, 5.3 (95% CI 1.7 -16.1), in 2006, 4.3 (95% CI 1.3 - 14.2) and in 2011, 3.8 (95% CI 1.3 - 11.2). The proportion of neonatal deaths attributable to LBW in the entire population declined by more than half, from 33.6% in 1995 to 15.3% in 2011. Neonatal mortality among LBW newborns also declined from 83.8% to 73.7% during the same period. CONCLUSION: Low birthweight contributes to a substantial proportion of neonatal deaths in Uganda. Although significant progress has been made to reduce newborn deaths, about three-quarters of all LBW neonates died in the neonatal period by 2011. This implies that the health system has been inadequate in its efforts to save LBW babies. A holistic strategy of community level interventions such as improved nutrition for pregnant mothers, prevention of teenage pregnancies, use of mosquito nets during pregnancy, antenatal care for all, adequate skilled care during birth to prevent birth asphyxia among LBW babies, and enhanced quality of postnatal care among others could effectively reduce the mortality numbers.

A prognostic 4-gene expression signature for squamous cell lung carcinoma.

Squamous cell lung carcinoma (SQCLC), a common and fatal subtype of lung cancer, caused lots of mortalities and showed different outcomes in prognosis. This study was to screen key genes and to figure a prognostic signature to cluster the patients with SQCLC. RNA-Seq data from 550 patients with SQCLC were downloaded from The Cancer Genome Atlas (TCGA). Genetically changed genes were identified and analyzed in univariate survival analysis. Genes significantly influencing prognosis were selected with frequency higher than 100 in lasso regression. Meanwhile, area under the curve (AUC) values and hazard ratios (HR) for seed genes were obtained with R Language. Functional enrichment analysis was performed and clustering effectiveness of the selected common gene set was analyzed with Kaplan-Meier. Finally, the stability and validity of the optimal clustering model were verified. A total of 7,222 genetically changed genes were screened, including 1,045 ones with p < 0.05, 1,746, p < 0.1, and 2,758, p < 0.2. The common gene sets with more than 100 frequencies were 14-Genes, 10-Genes and 6-Genes. Genes with p < 0.05 participated in positive regulation of ERK1 and ERK2 cascade, angiogenesis, platelet degranulation, cell-matrix adhesion, extracellular matrix organization, macrophage activation, and so on. A four-gene clustering model in 14-Genes (DPPA, TTTY16, TRIM58, HKDC1, ZNF589, ALDH7A1, LINC01426, IL19, LOC101928358, TMEM92, HRASLS, JPH1, LOC100288778, GCGR) was verified as the optimal. The discovery of four-gene clustering model in 14-Genes can cluster the patient samples effectively. This model would help predict the outcomes of patients with SQCLC then improve the treatment strategies.

TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan-Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients' outcomes and survival.

Anti-Inflammatory and Cancer-Preventive Potential of Chamomile (Matricaria chamomilla L.): A Comprehensive In Silico and In Vitro Study.

BACKGROUND AND AIM: Chamomile tea, renowned for its exquisite taste, has been appreciated for centuries not only for its flavor but also for its myriad health benefits. In this study, we investigated the preventive potential of chamomile (Matricaria chamomilla L.) towards cancer by focusing on its anti-inflammatory activity. METHODS AND RESULTS: A virtual drug screening of 212 phytochemicals from chamomile revealed ß-amyrin, ß-eudesmol, ß-sitosterol, apigenin, daucosterol, and myricetin as potent NF-κB inhibitors. The in silico results were verified through microscale thermophoresis, reporter cell line experiments, and flow cytometric determination of reactive oxygen species and mitochondrial membrane potential. An oncobiogram generated through comparison of 91 anticancer agents with known modes of action using the NCI tumor cell line panel revealed significant relationships of cytotoxic chamomile compounds, lupeol, and quercetin to microtubule inhibitors. This hypothesis was verified by confocal microscopy using α-tubulin-GFP-transfected U2OS cells and molecular docking of lupeol and quercetin to tubulins. Both compounds induced G2/M cell cycle arrest and necrosis rather than apoptosis. Interestingly, lupeol and quercetin were not involved in major mechanisms of resistance to established anticancer drugs (ABC transporters, TP53, or EGFR). Performing hierarchical cluster analyses of proteomic expression data of the NCI cell line panel identified two sets of 40 proteins determining sensitivity and resistance to lupeol and quercetin, further pointing to the multi-specific nature of chamomile compounds. Furthermore, lupeol, quercetin, and ß-amyrin inhibited the mRNA expression of the proinflammatory cytokines IL-1ß and IL6 in NF-κB reporter cells (HEK-Blue Null1). Moreover, Kaplan-Meier-based survival analyses with NF-κB as the target protein of these compounds were performed by mining the TCGA-based KM-Plotter repository with 7489 cancer patients. Renal clear cell carcinomas (grade 3, low mutational rate, low neoantigen load) were significantly associated with shorter survival of patients, indicating that these subgroups of tumors might benefit from NF-κB inhibition by chamomile compounds. CONCLUSION: This study revealed the potential of chamomile, positioning it as a promising preventive agent against inflammation and cancer. Further research and clinical studies are recommended.

Clinical significance and prospective mechanism of increased CDKN2A expression in small cell lung cancer.

BACKGROUND: Although it has been shown that cyclin dependent kinase inhibitor 2A (CDKN2A) plays a significant role in a number of malignancies, its clinicopathological value and function in small cell lung cancer (SCLC) is unclear and warrants additional research. METHODS: The clinical significance of CDKN2A expression in SCLC was examined by multiple methods, including comprehensive integration of mRNA level by high throughput data, Kaplan-Meier survival analysis for prognostic value, and validation of its protein expression using in-house immunohistochemistry. RESULTS: The expression of CDKN2A mRNA in 357 cases of SCLC was evidently higher than that in the control group (n = 525) combing the data from 20 research centers worldwide. The standardized mean difference (SMD) was 3.07, and the area under the curve (AUC) of summary receiver operating characteristic curve (sROC) was 0.97 for the overexpression of CDKN2A. ACC, COAD, KICH, KIRC, PCPG, PRAD, UCEC, UVM patients with higher CDKN2A expression had considerably worse overall survival rates than those with lower CDKN2A expression with the hazard ratio (HR) > 1. CONCLUSION: CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC.

Survival, growth and digestive functions after exposure to nanodiamonds - Transgenerational effects beyond contact time in house cricket strains.

The long-term exposure effects of nanodiamonds (NDs), spanning an organism's entire lifespan and continuing for subsequent generation, remain understudied. Most research has focused on evaluating their biological impacts on cell lines and selected organisms, typically over short exposure durations lasting hours or days. The study aimed to assess growth, mortality, and digestive functions in wild (H) and long-lived (D) strains of Acheta domesticus (Insecta: Orthoptera) after two-generational exposure to NDs in concentrations of 0.2 or 2 mg kg-1 of food, followed by their elimination in the third generation. NDs induced subtle stimulating effect that depended on the strain and generation. In the first generation, more such responses occurred in the H than in the D strain. In the first generation of H strain insects, contact with NDs increased survival, stimulated the growth of young larvae, and the activity of most digestive enzymes in mature adults. The same doses and exposure time did not cause similar effects in the D strain. In the first generation of D strain insects, survival and growth were unaffected by NDs, whereas, in the second generation, significant stimulation of those parameters was visible. Selection towards longevity appears to support higher resistance of the insects to exposure to additional stressor, at least in the first generation. The cessation of ND exposure in the third generation caused potentially harmful changes, which included, e.g., decreased survival probability in H strain insects, slowed growth of both strains, as well as changes in heterochromatin density and distribution in nuclei of the gut cells in both strains. Such a reaction may suggest the involvement of epigenetic inheritance mechanisms, which may become inadequate after the stress factor is removed.

Effect of Novel Inflammatory Biomarkers on Adverse Outcomes in Patients with Interstitial Lung Disease and Pneumonia: A Multicenter Retrospective Cohort Study.

BACKGROUND: Interstitial lung disease frequently coincides with pneumonia in clinical settings, and both conditions are closely associated with immunoinflammation. The Systemic Immune Inflammatory Index (SII) is a recently identified marker, and its connection to the prognosis of individuals suffering from interstitial lung disease and concurrent pneumonia remains unclear. The objective of this study was to scrutinize the correlation between varying SII levels and unfavorable outcomes in patients grappling with interstitial lung disease complicated by pneumonia. METHODS: This study encompassed a retrospective multicenter cohort of 324 patients diagnosed with interstitial lung disease and pneumonia, all receiving glucocorticoid treatment during their hospitalization. We initially conducted ROC analysis to determine the optimal SII threshold. Subsequently, we examined disparities in clinical symptoms, physical signs, clinical test data, and other clinical attributes among patients with differing SII levels. Later, we employed the Kaplan-Meier survival curve method to assess the association between distinct SII levels and the 30-day and 90-day mortality rates in patients dealing with interstitial lung disease complicated by pneumonia. Finally, a Cox regression model was employed to identify factors influencing adverse prognosis in these patients. RESULTS AND DISCUSSION: The findings demonstrated that the optimal SII threshold for predicting 30-day mortality was 1416.97, with an AUC of 0.633 (95% CI: 0.559-0.708) and a P value of <0.001. For 90-day mortality, the optimal SII threshold was 994.59, yielding an AUC of 0.628 (95% CI: 0.56-0.697) and a P value of <0.001. Noteworthy statistical distinctions emerged in dyspnea, cyanosis, and oxygenation index among patients with varying SII levels. Additionally, invasive mechanical ventilation, non-invasive ventilation, and extended infection duration independently constituted 30-day and 90-day mortality risk factors. Elevated heart rate and higher SII levels emerged as independent risk factors for 90-day mortality. CONCLUSION: To some extent, SII levels exhibit correlations with the clinical manifestations in patients grappling with interstitial lung disease complicated by pneumonia. Notably, a high SII level is an independent predictor for an unfavorable prognosis in these patients. Nevertheless, these findings warrant further validation through prospective cohort studies.

Determining the Time Required to Achieve Clinically Significant Outcomes on the PROMIS Upper Extremity Questionnaire After Arthroscopic Rotator Cuff Repair.

Background: Clinically significant outcome (CSO) thresholds for the Patient-Reported Outcome Measurement Information System-Upper Extremity (PROMIS-UE) score have been previously defined after arthroscopic rotator cuff repair (RCR). However, the time required to achieve CSOs for the PROMIS-UE score is unknown. Purpose: To (1) determine the time required to achieve the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and Patient Acceptable Symptom State (PASS) score thresholds after RCR for the PROMIS-UE questionnaire and (2) identify patient factors associated with earlier or delayed achievement of these clinical benchmarks. Study Design: Case-control study; Level of evidence, 3. Methods: A prospectively maintained institutional database was retrospectively reviewed for consecutive patients who underwent RCR between January 2018 and January 2019. Patients were included if they completed the PROMIS-UE questionnaire both preoperatively and at standardized postoperative time intervals: 5 to 7 months (6-month time point), 11 to 13 months (1-year time point), and ≥23 months (2-year time point). Kaplan-Meier survival curves with interval censoring were used to define the cumulative percentage of patients who achieved the MCID, SCB, and PASS. Patient variables associated with earlier or delayed achievement of the MCID, SCB, and PASS were determined using Weibull parametric survival regression analysis. Results: Included were 105 patients undergoing RCR (age, 57.3 ± 10.3 years; body mass index, 31.5 ± 6.1 kg/m2). By 2-year follow-up, the cumulative percentage of patients achieving the MCID, SCB, and PASS was 86.7%, 76.2%, and 74.3%, respectively. The mean time required to reach the MCID, SCB, and PASS score thresholds was 9.5 ± 3.8, 10.3 ± 4.4, and 9.8 ± 4.6 months, respectively. Factors associated with delayed achievement of CSOs included greater baseline PROMIS-UE score (MCID and SCB) and workers' compensation insurance (PASS). Greater baseline PROMIS-UE scores were associated with earlier achievement of the PASS. Conclusion: Most patients achieved CSOs for the PROMIS-UE within 12 months of RCR. Patient-specific factors found to be associated with earlier or delayed achievement of CSOs can be used to inform patient discussions on the expected timeline for recovery after RCR.

A multicentre comparative analysis of fixation versus revision surgery for periprosthetic femoral fractures following total hip arthroplasty with a cemented polished taper-slip femoral component.

AIMS: The aim of this study was to compare open reduction and internal fixation (ORIF) with revision surgery for the surgical management of Unified Classification System (UCS) type B periprosthetic femoral fractures around cemented polished taper-slip femoral components following primary total hip arthroplasty (THA). METHODS: Data were collected for patients admitted to five UK centres. The primary outcome measure was the two-year reoperation rate. Secondary outcomes were time to surgery, transfusion requirements, critical care requirements, length of stay, two-year local complication rates, six-month systemic complication rates, and mortality rates. Comparisons were made by the form of treatment (ORIF vs revision) and UCS type (B1 vs B2/B3). Kaplan-Meier survival analysis was performed with two-year reoperation for any reason as the endpoint. RESULTS: A total of 317 periprosthetic fractures (in 317 patients) with a median follow-up of 3.6 years (interquartile range (IQR) 2.0 to 5.4) were included. The fractures were type B1 in 133 (42.0%), B2 in 170 (53.6%), and B3 in 14 patients (4.4%). ORIF was performed in 167 (52.7%) and revision in 150 patients (47.3%). The two-year reoperation rate (15.3% vs 7.2%; p = 0.021), time to surgery (4.0 days (IQR 2.0 to 7.0) vs 2.0 days (IQR 1.0 to 4.0); p < 0.001), transfusion requirements (55 patients (36.7%) vs 42 patients (25.1%); p = 0.026), critical care requirements (36 patients (24.0%) vs seven patients (4.2%); p < 0.001) and two-year local complication rates (26.7% vs 9.0%; p < 0.001) were significantly higher in the revision group. The two-year rate of survival was significantly higher for ORIF (91.9% (standard error (SE) 0.023%) vs 83.9% (SE 0.031%); p = 0.032) compared with revision. For B1 fractures, the two-year reoperation rate was significantly higher for revision compared with ORIF (29.4% vs 6.0%; p = 0.002) but this was similar for B2 and B3 fractures (9.8% vs 13.5%; p = 0.341). The most common indication for reoperation after revision was dislocation (12 patients; 8.0%). CONCLUSION: Revision surgery has higher reoperation rates, longer surgical waiting times, higher transfusion requirements, and higher critical care requirements than ORIF in the management of periprosthetic fractures around polished taper-slip femoral components after THA. ORIF is a safe option providing anatomical reconstruction is achievable.Cite this article: Bone Joint J 2023;105-B(2):124-134.

Factors Affecting Final Surgical Outcome of Combined Trabeculotomy-Trabeculectomy in Primary Congenital Glaucoma.

PURPOSE: To evaluate different pre-operative variables on the success of combined trabeculotomy-trabeculectomy (CTT) surgery in patients with primary congenital glaucoma (PCG) to predict those at higher risk for surgical failure and for proper parent counseling. PATIENTS AND METHODS: Sixty-three eyes of patients with PCG were treated either with CTT without augmentation, or CTT augmented with mitomycin-C (0.2 mg/mL) in both subconjunctival space and under scleral flap for 3 minutes, or with CTT augmented with a collagen implant under both the scleral flap and the conjunctiva. Cases showed surgical failure was reported and evaluated in relation to different pre-operative variables. RESULTS: Complete success (IOP ≤21 mmHg) was achieved in 52 cases (82.5%). Cumulative success probability was calculated using Kaplan-Meier survival analysis, proving that higher pre-operative intraocular pressure (IOP) was associated with higher failure rates (28.6% for pre-operative IOP ≥30 mmHg versus 4.8% for IOP <30 mmHg), with P value = 0.007. CONCLUSION: CTT is an effective surgical intervention in PCG patients without sight threatening complications. Univariate survival analysis showed higher rates of surgical failure in patients with higher pre-operative IOP, while other pre-operative variables were irrelevant.

Impact of Treating Age-Related Macular Degeneration before Visual Function Is Impaired.

Visual outcomes of age-related macular degeneration (AMD) have substantially improved via anti-vascular endothelial growth factor (anti-VEGF) therapy. However, the treatment effects vary among individuals. Medical charts of 104 eyes (104 patients) with AMD, treated with anti-VEGF drugs and followed up for 12−36 months, were retrospectively analyzed. Logistic regression analyses adjusted for age showed that eyes with an initial best-corrected visual acuity (BCVA) < 0.3 in the logarithm of the minimum angle of resolution (logMAR) were a positive predictor (odds ratio = 3.172; 95% confidence interval [CI] = 1.029−9.783; p = 0.045), and the presence of initial fibrovascular pigment epithelial detachment (PED) was a negative predictor (0.222; 0.078−0.637; p = 0.005) of maintained or improved BCVA at the final visit. Kaplan−Meier survival analysis showed that eyes with an initial BCVA < 0.3 (Cox hazard ratio = 2.947; 95% CI = 1.047−8.289; p = 0.041) had a better survival rate after adjusting for age when failure was defined as a BCVA reduction ≥ 0.2 of logMAR. Eyes with an initial BCVA < 0.3 belonged to younger patients; more frequently had subretinal fluid as an exudative change; and less frequently had intraretinal fluid, submacular hemorrhage, and fibrovascular PED. Initiating anti-VEGF treatment before BCVA declines and advanced lesions develop would afford better visual outcomes for AMD eyes in the real-world clinic, although further analyses are required.

How long do tympanostomy ventilation tubes last in pediatric patients with otitis media with effusion or adhesion? A study using Kaplan-Meier survival analysis.

OBJECTIVE: The purpose of this study was to evaluate the functional duration and survival rate of tympanostomy ventilation tubes and the complications associated with their use in pediatric patients who underwent tube insertion for otitis media with effusion (OME). Complications were analyzed including recurrence and tympanic membrane perforation after the tube removal or extrusion. METHODS: Altogether, 447 ears from 234 pediatric patients younger than 15 years of age were studied retrospectively. All patients had undergone long-term tympanostomy ventilation tube: the Goode T-tube insertion for OME at the Osaka Women's and Children's Hospital, which is the pediatrics specialty hospital between April 2014 and March 2016. They were typically followed up every 3-4 months or more frequently if necessary due to otorrhea or tube infection. Subsequently, the tube duration, survival rates of the tube especially at 22 months after insertion defined as "full-term placement", and the rates of recurrence and perforation were calculated and statistically evaluated. RESULTS: Of 447 ears, 335 ears from 184 patients underwent their first tube insertion, and 112 ears from 64 patients underwent their second or subsequent tube insertion within the targeted period. Two hundred ears from 106 patients were associated with a cleft palate. The survival rate at full-term placement was 51.7%. The recurrence rate was 56.3%, and the rate of the tympanic perforation was 8.5%. CONCLUSIONS: Approximately half of the tubes survived for 22 months. The perforation rate was relatively low; however, recurrence of OME was seen in more than half the ears.

Delirium-related factors and their prognostic value in patients undergoing craniotomy for brain metastasis.

Background: Delirium is characterized by acute brain dysfunction. Although delirium significantly affects the quality of life of patients with brain metastases, little is known about delirium in patients who undergo craniotomy for brain metastases. This study aimed to identify the factors influencing the occurrence of delirium following craniotomy for brain metastases and determine its impact on patient prognosis. Method: A total of 153 patients who underwent craniotomy for brain metastases between March 2013 and December 2020 were evaluated for clinical and radiological factors related to the occurrence of delirium. Statistical analysis was conducted by dividing the patients into two groups based on the presence of delirium, and statistical significance was confirmed by adjusting the clinical characteristics of the patients with brain metastases using propensity score matching (PSM). The effect of delirium on patient survival was subsequently evaluated using Kaplan-Meier analysis. Results: Of 153 patients, 14 (9.2%) had delirium. Age (P = 0.002), sex (P = 0.007), and presence of postoperative hematoma (P = 0.001) were significantly different between the delirium and non-delirium groups. When the matched patients (14 patients in each group) were compared using PSM, postoperative hematoma showed a statistically significant difference (P = 0.036) between the delirium and non-delirium groups. Kaplan-Meier survival analysis revealed that the delirium group had poorer prognosis (log-rank score of 0.0032) than the non-delirium group. Conclusion: In addition to the previously identified factors, postoperative hematoma was identified as a strong predictor of postoperative delirium. Also, the negative impact of delirium on patient prognosis including low survival rate was confirmed.

Clinical outcome in total hip arthroplasty for septic sequelae in childhood : a retrospective study.

AIMS: Adult patients with history of childhood infection pose a surgical challenge for total hip arthroplasty (THA) due to distorted bony anatomy, soft-tissue contractures, risk of reinfection, and relatively younger age. Therefore, the purpose of the present study was to determine clinical outcome, reinfection rate, and complications in patients with septic sequelae after THA. METHODS: A retrospective analysis was conducted of 91 cementless THAs (57 male and 34 female) performed between 2008 and 2017 in patients who had history of hip infection during childhood. Clinical outcome was measured using Harris Hip Score (HHS) and Modified Merle d'Aubigne and Postel (MAP) score, and quality of life (QOL) using 12-Item Short Form Health Survey Questionnaire (SF-12) components: Physical Component Score (PCS) and Mental Component Score (MCS); limb length discrepancy (LLD) and radiological assessment of the prosthesis was performed at the latest follow-up. Reinfection and revision surgery after THA for any reason was documented. RESULTS: There was significant improvement in HHS, Modified Merle d'Aubigne Postel hip score, and QOL index SF 12-PCS and MCS (p < 0.001) and there was no case of reinfection reported during the follow-up. The minimum follow-up for the study was three years with a mean of 6.5 (SD 2.3; 3 to 12). LLD decreased from a mean of 3.3 cm (SD 1) to 0.9 cm (SD 0.8) during follow-up. One patient required revision surgery for femoral component loosening. Kaplan-Meier survival analysis estimated revision-free survivorship of 100% at the end of five years and 96.9% (95% confidence interval 79.8 to 99.6) at the end of ten years. CONCLUSION: We found that cementless THA results in good to excellent functional outcomes in patients with a prior history of childhood infection. There is an exceedingly low rate of risk of reinfection in these patients, even though complications are not uncommon. Cite this article: Bone Jt Open 2022;3(4):314-320.

Femoral head collapse rate among Japanese patients with pre-collapse osteonecrosis of the femoral head.

OBJECTIVE: In this study, we aimed to elucidate the relationship between the duration from diagnosis to femoral head collapse and the collapse rate among patients with pre-collapse osteonecrosis of the femoral head (ONFH). METHODS: In this retrospective, observational, multicenter study, we analyzed 268 patients diagnosed with ONFH and classified them using the Japanese Investigation Committee classification. The primary endpoint was duration from the time of diagnosis to femoral head collapse for each type of ONFH. RESULTS: The 12-, 24-, and 36-month collapse rates among participants were 0%, 0%, and 0% for type A, respectively; 0%, 2.0%, and 10.8% for type B, respectively; 25.5%, 40.8%, and 48.5% for type C-1, respectively; and 57.4%, 70.3%, and 76.7% for type C-2 ONFH, respectively. A comparison of unilateral and bilateral ONFH, using Kaplan-Meier survival curves demonstrated similar collapse rates. CONCLUSIONS: The lowest collapse rate was observed for ONFH type A, followed by types B, C-1, and C-2. Additionally, a direct association was observed between the collapse rate and location of the osteonecrotic lesion on the weight-bearing surface.

High nuclear expression of HIF1α, synergizing with inactivation of LIMD1 and VHL, portray worst prognosis among the bladder cancer patients: association with arsenic prevalence.

PURPOSE: Our study was aimed to understand the importance of LIMD1-VHL-HIF1α pathway in development of bladder carcinoma (BlCa) in association with arsenic prevalence. METHODS: At first, the mRNA expression pattern of the genes of this pathway (LIMD1, VHL and HIF1α) was checked in GEO datasets and in our samples. Next, genetic and epigenetic profiling of LIMD1 and VHL was done in our sample pool, validated in T24 BlCa cell line. The results were next correlated with various clinico-pathological parameters. RESULTS: Differential under-expression of LIMD1 and VHL genes was found in muscle-invasive BlCa (MIBC) in comparison to non-muscle-invasive BlCa (NMIBC). However, HIF1α protein, but mRNA, was found to be overexpressed among the MIBC samples; depicting the probability of HIF1α protein stabilization. Analysis of genetic and epigenetic profiles of LIMD1 and VHL exposed a frequent promoter methylation of LIMD1 gene in MIBC samples. Further, in-depth look into the results unveiled that the high nuclear expression of HIF1α was significantly correlated with genetic alterations of LIMD1, alone or in combination with VHL. Moreover, treating the T24 cells with a de-methylating agent (5-aza-2'-deoxycytidine) re-expressed the methylated LIMD1 and VHL genes, which in turn, reduced the HIF1α protein level significantly. Additionally, patients with high arsenic content (> 112 ng/g, AsH) seemed to have recurrent promoter methylation in LIMD1, as well as co-methylation/alteration of LIMD1 and VHL gene. Lastly, high nuclear expression of HIF1α in association with co-alteration of VHL and LIMD1 showed the worst overall survival (OS) among the patients. CONCLUSION: To conclude, MIBC samples portrayed higher alterations in VHL and LIMD1, thereby, stabilizing HIF1α protein and lowering the OS of patients.

Prognosis and Survival Analysis of 922,317 Lung Cancer Patients from the US Based on the Most Recent Data from the SEER Database (April 15, 2021).

BACKGROUND: On April 15, 2021, the Surveillance, Epidemiology, and End Results (SEER) database released the latest lung cancer follow-up data. We selected 922,317 lung cancer patients diagnosed from 2000 to 2017 for survival analysis to provide updated data for lung cancer researchers. RESEARCH QUESTION: This study explored the latest trends of survival time in terms of gender, race, nationality, age, income, address, histological type and primary site. STUDY DESIGN AND METHODS: The SEER database covers 27.8% of the US population. We used life table, Kaplan-Meier, log-rank, Breslow and Tarone-Ware tests to calculate survival rate, time, and curve and to compare differences in survival distribution. We performed univariate and multivariate Cox proportional hazards analyses. RESULTS: The median survival time of all lung cancer patients diagnosed in 2017 increased by 41.72% compared to 2000. Median survival time of female patients diagnosed in 2017 increased by 70.94% compared to 2000. Median survival time of those diagnosed in 2017 for different primary sites was as follows: right middle lobe was the longest, then left lower lobe, right upper lobe, right lower lobe, and left upper lobe. Lung cancer patients older than 75 years had a significantly shorter median survival time. Patients living in metropolitan areas of 250,000 to 1 million had a longer median survival time. Median survival time in the adenocarcinoma group was significantly greater than other patients. Median survival of Asian and other races diagnosed in 2017 was 97.87% higher than those diagnosed in 2000. Survival rate of lung cancer increased gradually with the year of diagnosis. INTERPRETATION: The rapid improvement of the prognosis of female and young lung cancer patients contributes to the improvement of the overall prognosis. Primary lung cancer in the right middle lobe has the best prognosis.