Identifying Independent Predictors of Short-Term Postoperative Morbidity in Patients Undergoing Cranioplasty.

BACKGROUND: The present study intends to identify independent predictors of short-term postoperative complications and health utilization in patients undergoing cranioplasty. METHODS: Demographic, clinical, and intraoperative characteristics were collected for each patient undergoing cranioplasty in the National Surgery Quality Improvement Program database from 2011 to 2020. The 30-day outcomes analyzed were medical complications, wound complications, return to the operating room, extended hospital stay, and non-home discharge. Bivariate analyses were initially used to identify variables that yielded a P value less than 0.2 which were subsequently analyzed in a multivariate logistic regression to identify independent predictors of the aforementioned outcomes. RESULTS: In total, 2316 patients undergoing cranioplasty were included in the analysis. Increased operative time and totally dependent functional status significantly increased odds of returning to the operating room. Increased age, operative time, cranioplasty size >5 cm, and various comorbidities were associated with increased odds of non-home discharge. Bleeding disorders were independently associated with increased odds of wound complications. Increased age, operative time, cranioplasty size >5 cm, and several medical history features predisposed to medical complications. Demographic characteristics, including age and race, along with various operative and medical history characteristics were associated with increased odds of extended length of stay. CONCLUSIONS: Identification of risk factors can help guide preoperative risk management in cranioplasty.

"Like a ticking time bomb": the persistence of trauma in the HIV diagnosis experience among black men who have sex with men in New York City.

BACKGROUND: Black men who have sex with men (MSM) are disproportionately affected by HIV compared to almost every other demographic group in the country and have worse outcomes along the care continuum. Diagnosis is a critical juncture. This study aims to explore the impact and meaning of an HIV diagnosis for Black MSM, and how this has changed over time, both for the individual's experience living with HIV as well as for Black MSM in general. METHODS: From 2017 to 2018, we conducted in-depth interviews with 16 black MSM living with HIV in New York City diagnosed between 1985 and 2016. RESULTS: Inductive analysis of the qualitative data allowed three major themes to emerge: diagnosis trauma, lack of patient -centeredness in the healthcare system, and acceptance of HIV diagnosis over time. CONCLUSIONS: This small pilot study signals that an HIV diagnosis experience possibly remains traumatic for black MSM even in the era of highly effective ART, and they often perceive a lack of patient-centeredness in the delivery of a new diagnosis. This has persisted over time. In most cases, black MSM in our sample overcame this trauma due to self-motivation, social support and seeking out and fostering trusting relationships with their HIV provider and the healthcare system.

Identification of potential transmembrane protease serine 4 inhibitors as anti-cancer agents by integrated computational approach.

Transmembrane protease serine 4 is a well known cell surface protease facilitating the extracellular matrix degradation and epithelial mesenchymal transition in hepatocellular carcinoma. Henceforth targeting transmembrane protease serine 4 is strongly believed to provide therapeutic intervention against hepatocellular carcinoma. Owing to lack of crystal structure for human transmembrane protease serine 4, we predicted its three dimensional structure for the first time in this study. Experimentally proven inhibitor-Tyroserleutide (TSL) against hepatocellular carcinoma via transmembrane protease serine 4 was used as a benchmark to identify structurally similar candidates from PubChem database to create the TSL library. Virtual screening of TSL library against modeled transmembrane protease serine 4 revealed the top four potential inhibitors. Further binding free energy (ΔGbind) analysis of the potential inhibitors revealed the best potential lead compound against transmembrane protease serine 4. Drug likeliness nature of the top four potential hits were additionally analyzed in comparison to TSL to confirm on the best potential lead compound with the highest % of human oral absorption. Consequently, e-pharmacophore mapping of the best potential lead compound yielded a six point feature. It was observed to contain four hydrogen bond donor sites (D), one positively ionizable site (P) and one aromatic ring (R). Such e-pharmacophore insight obtained from structural determinants by integrated computational analysis could serve as a framework for further advancement of drug discovery process of new anti-cancer agents with less toxicity and high specificity targeting transmembrane protease serine 4 and hepatocellular carcinoma.

Delayed Haemothorax Resulting from Indwelling Right Internal Jugular Central Venous Catheter: A Rare Complication.

Haemothorax is an uncommon and serious complication, occurring most often during or immediately after percutaneous internal jugular and subclavian vein catheterizations. Delayed haemothorax is a rare complication, especially following right-sided catheterization. We report a case of acute yellow phosphorus poisoning with acute liver failure (resulting from rat killer paste ingestion) in a 28-year-old male who developed right-sided haemothorax eight days after placement of right internal jugular central venous catheter. The proposed pathogenesis involves vascular wall erosion by the indwelling catheter tip. Awareness of this complication perhaps avoids unnecessary investigations for other causes of haemothorax such as pulmonary embolism.

A covalent creatine kinase inhibitor ablates glioblastoma migration and sensitizes tumors to oxidative stress.

Glioblastoma is a Grade 4 primary brain tumor defined by therapy resistance, diffuse infiltration, and near-uniform lethality. The underlying mechanisms are unknown, and no treatment has been curative. Using a recently developed creatine kinase inhibitor (CKi), we explored the role of this inhibitor on GBM biology in vitro. While CKi minimally impacted GBM cell proliferation and viability, it significantly affected migration. In established GBM cell lines and patient-derived xenografts, CKi ablated both the migration and invasion of GBM cells. CKi also hindered radiation-induced migration. RNA-seq revealed a decrease in invasion-related genes, with an unexpected increase in glutathione metabolism and ferroptosis protection genes post-CKi treatment. The effects of CKi could be reversed by the addition of cell-permeable glutathione. Carbon-13 metabolite tracing indicated heightened glutathione biosynthesis post-CKi treatment. Combinatorial CKi blockade and glutathione inhibition or ferroptosis activation abrogated cell survival. Our data demonstrated that CKi perturbs promigratory and anti-ferroptotic roles in GBM, identifying the creatine kinase axis as a druggable target for GBM treatment.

Comparative evaluation of autologous platelet-rich fibrin and platelet-rich plasma in the treatment of mandibular degree II furcation defects: a randomized controlled clinical trial.

BACKGROUND: The treatment of molar furcation defects remains a considerable challenge in clinical practice. The identification of clinical measurements influential to treatment outcomes is critical to optimize the results of surgical periodontal therapy. The present study aimed to explore the clinical and radiographical effectiveness of autologous platelet-rich fibrin (PRF) and autologous platelet-rich plasma (PRP) in the treatment of mandibular degree II furcation defects in subjects with chronic periodontitis. MATERIAL AND METHODS: Seventy-two mandibular degree II furcation defects were treated with either autologous PRF with open flap debridement (OFD; 24 defects) or autologous PRP with OFD (25), or OFD alone (23). Clinical and radiological parameters such as probing depth, relative vertical clinical attachment level and horizontal clinical attachment level along with gingival marginal level were recorded at baseline and 9 mo postoperatively. RESULTS: All clinical and radiographic parameters showed statistically significant improvement at both the test sites (PRF with OFD and PRP with OFD) compared to those with OFD alone. Relative vertical clinical attachment level gain was also greater in PRF (2.87 ± 0.85 mm) and PRP (2.71 ± 1.04 mm) sites as compared to control site (1.37 ± 0.58 mm), and relative horizontal clinical attachment level gain was statistically significantly greater in both PRF and PRP than in the control group. CONCLUSIONS: The use of autologous PRF or PRP were both effective in the treatment of furcation defects with uneventful healing of sites.

Development, Validation, and Impact of Patient Information Booklet for Gamma Knife Radiosurgery.

Background: The inadequate awareness in the general population is a primary concern for the management of various neurosurgical ailments treated with gamma knife radiosurgery (GKRS). Objective: Our study aimed to assess the written patient information by focusing on readability, recall, communication, compliance, and patient satisfaction. Methodology: The senior author formulated disease-specific patient information booklets. The booklets comprised two segments: general information about GKRS and disease-specific information. The common themes for discussion were "What is your disease?", "What is gamma knife radiosurgery?", "What are the alternatives to gamma knife radiosurgery," "The benefits of gamma knife radiosurgery," "About gamma knife radiosurgery," "Recovering from gamma knife radiosurgery," "Follow up," "What are the risks," and "Contact." The booklet was emailed after the first consultation to 102 patients. Patients' socioeconomic status and comprehensibility were assessed on validated scoring. Post-GKRS, we emailed a custom-made Google feedback survey of 10 leading questions about the role of patient information booklet in educating and decision-making process. We tried to assess if the booklet helped the patient understand the disease and treatment options. Results: In total, 94% of patients read it thoroughly and understood it to their satisfaction. They also shared and discussed the information booklet with their family members and relatives (92%). Furthermore, 96% of patients found the disease-specific information informative. For 83% of patients, the information brochure cleared the doubts regarding the GKRS completely. For 66% of patients, their expectations met the reality. In addition, 94% of patients still recommended giving the booklet to the patients. All high, upper- and middle-class responders were happy and content with the patient information booklet. In contrast, 18 (90%) of the lower middle class and 2 (66.7%) of the lower class considered the information useful to the patients. Also, 90% patients found the language of the patient information booklet comprehensible and not too technical to understand. Conclusions: An essential component of disease management is to relieve the anxiety and confusion in the patient's mind and help one choose a treatment modality among the available options. A patient-centric booklet helps impart knowledge, clears doubts, and provides an opportunity to discuss options with family members.

A novel BRAF::PTPRN2 fusion in meningioma: a case report.

Gene fusion events have been linked to oncogenesis in many cancers. However, gene fusions in meningioma are understudied compared to somatic mutations, chromosomal gains/losses, and epigenetic changes. Fusions involving B-raf proto-oncogene, serine/threonine kinase (BRAF) are subtypes of oncogenic BRAF genetic abnormalities that have been reported in certain cases of brain tumors, such as pilocytic astrocytomas. However, BRAF fusions have not been recognized in meningioma. We present the case of an adult female presenting with episodic partial seizures characterized by déjà vu, confusion, and cognitive changes. Brain imaging revealed a cavernous sinus and sphenoid wing mass and she underwent resection. Histopathology revealed a World Health Organization (WHO) grade 1 meningioma. Genetic profiling with next generation sequencing and microarray analysis revealed an in-frame BRAF::PTPRN2 fusion affecting the BRAF kinase domain as well as chromothripsis of chromosome 7q resulting in multiple segmental gains and losses including amplifications of cyclin dependent kinase 6 (CDK6), tyrosine protein-kinase Met (MET), and smoothened (SMO). Elevated pERK staining in tumor cells provided evidence of activated mitogen-activated protein kinase (MAPK) signaling. This report raises the possibility that gene fusion events may be involved in meningioma pathogenesis and warrant further investigation.

Adolescent Idiopathic Scoliosis and Pregnancy.

Objective This study examined the interaction between adolescent idiopathic scoliosis (AIS) and pregnancy, focusing on pregnancy outcomes, changes in back pain, and anesthesia use. Methods A retrospective analysis was conducted on adult patients with AIS who gave birth at our institution between 2006 and 2022. Results A total of 163 AIS patients with 263 pregnancies were included. The median age at delivery was 33 (range 18 to 50) years. Among 157 patients with information on prior scoliosis treatment, 66.9% had not received treatment, 20.4% had undergone spinal fusion, and 12.7% had received bracing. Of the 260 pregnancies with available data, 90.4% were delivered at term and 8.5% were preterm. Of the 257 pregnancies with information on anesthesia type, 35.0% received epidural anesthesia, 17.9% received spinal anesthesia, 37.7% received combined spinal and epidural anesthesia, 8.2% received no anesthesia, and 1.2% received intravenous or general anesthesia. Difficulty administering neuraxial anesthesia was reported in 6.1% of cases, and these patients were less likely to receive combined spinal and epidural anesthesia (6.3% versus 39.8%, p = 0.0123). Among 116 cases with recorded back pain during pregnancy, 67.2% reported increased pain, 31.9% reported similar pain, and one patient reported decreased pain. Of the 16 patients with pre and postpartum radiographs, eight showed a Cobb angle increase ≥ 3°, with five patients having an increase ≥ 5°. Conclusions Pregnancy can exacerbate back pain and pose challenges for neuraxial anesthesia in some AIS patients. Further large-scale, multi-institutional studies with standardized data collection are needed to fully understand the impact of pregnancy on AIS.

Post-Surgical Prognosis of Patients with Pineoblastoma: A Systematic Review and Individual Patient Data Analysis with Trends over Time.

Most of the literature on pineoblastoma consists of case reports and single-institution series. The goal of this systematic review and individual patient data (IPD) analysis was to summarize the existing literature, identify factors associated with overall survival (OS), and provide a contemporary update on prognosis for patients with pineoblastoma. Forty-four studies were identified with 298 patients having IPD. Kaplan-Meier analyses were used to report survival outcomes based on age, tumor metastases, extent of resection (EOR), adjuvant therapy, and publication year. Cox regression was performed to identify independent predictors of time to mortality. Multivariable recursive partitioning analysis was used to identify the most important subgroups associated with mortality. Patients were classified based on publication year before and after the last systematic review on this topic (pre-2012 and 2012 onwards) and compared using univariate and multivariable analyses. This study demonstrates that EOR less-than-gross total resection, metastatic presentation, adjuvant chemotherapy without radiation, and tumor presentation in children less than three years old are associated with poorer prognosis. Since 2012, the 5-year actuarial OS has improved from 32.8% to 56.1%, which remained significant even after accounting for EOR, age, and adjuvant therapy. Pineoblastoma remains a severe rare disease, but survival outcomes are improving.

Orbital Rosai-Dorfman disease initially diagnosed as IgG4-related disease: a case report.

Inflammatory orbital lesions include a broad list of diagnoses, many of them with overlapping clinical and radiographic features. They often present a diagnostic conundrum, even to the most experienced orbital specialist, thus placing considerable weight on surgical biopsy and histopathological analysis. However, histopathological diagnosis is also inherently challenging due to the rarity of these lesions and the overlaps in histologic appearance among distinct disease entities. We herein present the case of an adolescent male with a subacutely progressive orbital mass that generated a significant diagnostic dilemma. Early orbital biopsy was consistent with a benign fibro-inflammatory lesion, but corticosteroid therapy was ineffective in halting disease progression. After an initial substantial surgical debulking, histopathological analysis revealed several key features consistent with IgG4-related disease (IgG4-RD), a systemic fibro-inflammatory process typically accompanied by multifocal tumor-like lesions. Surprisingly, within months, there was clear evidence of clinical and radiographic disease progression despite second-line rituximab treatment, prompting a second surgical debulking. This final specimen displayed distinctive features of Rosai-Dorfman disease (RDD), a systemic inflammatory disease characterized by uncontrolled histiocytic proliferation. Interestingly, certain features of this re-excision specimen were still reminiscent of IgG4-RD, which not only reflects the difficulty in differentiating RDD from IgG4-RD in select cases, but also illustrates that these diagnoses may exist along a spectrum that likely reflects a common underlying pathogenetic mechanism. This case emphasizes the importance of surgical biopsy or resection and histopathological analysis in diagnosing-and, ultimately, treating-rare, systemic inflammatory diseases involving the orbit, and, furthermore, highlights the shared histopathological features between RDD and IgG4-RD.

Does elective re-siting of intravenous cannulae decrease peripheral thrombophlebitis? A randomized controlled study.

BACKGROUND: Peripheral venous thrombophlebitis (PVT) is a common complication of intravenous cannulation, occurring in about 30% of patients. We evaluated the effect of elective re-siting of intravenous cannulae every 48 hours on the incidence and severity of PVT in patients receiving intravenous fluids/drugs. METHODS: We randomized 42 patients who were admitted for major abdominal surgery to either the control or study group (n = 21 in either group). Informed consent was obtained from all of them. Cannulae in the control group were removed only if the site became painful, the cannula got dislodged or there were signs and symptoms suggestive of PVT, namely pain, erythema, swelling, excessive warmth or a palpable venous cord. Cannulae in the study group were changed and re-sited electively every 48 hours. All the patients were examined every 24 hours for signs and symptoms of PVT at the current and previous sites of infusion. RESULTS: The incidence of PVT was 100% (21/21) in the control group and only 9.5% (2/21) in the study group (p < 0.0001). The severity of PVT was also less in the study group compared with that in the control group. Day-wise correlation of the incidence of PVT showed that 82.6% of the episodes of PVT occurred on day 3. CONCLUSION: Elective re-siting of intravenous cannulae every 48 hours results in a significant reduction in the incidence and severity of PVT. We recommend that this should be adopted as standard practice in managing all patients who require prolonged intravenous therapy.

Beyond electrostatics: Antimicrobial peptide selectivity and the influence of cholesterol-mediated fluidity and lipid chain length on protegrin-1 activity.

Antimicrobial peptides (AMPs) are a promising class of innate host defense molecules for next-generation antibiotics, as they uniquely target and permeabilize membranes of pathogens. This selectivity has been explained by the electrostatic attraction between these predominantly cationic peptides and the bacterial membrane, which is heavily populated with anionic lipids. However, AMP-resistant bacteria have non-electrostatic countermeasures that modulate membrane rigidity and thickness. We explore how variations in physical properties affect the membrane affinity and disruption process of protegrin-1 (PG-1) in phosphatidylcholine (PC) membranes with altered lipid packing densities and thicknesses. From isothermal titration calorimetry and atomic force microscopy, our results showed that PG-1 could no longer insert into membranes of increasing cholesterol amounts nor into monounsaturated PC membranes of increasing thicknesses with similar fluidities. Prevention of PG-1's incorporation consequently made the membranes more resistant to peptide-induced structural transformations like pore formation. Our study provides evidence that AMP affinity and activity are strongly correlated with the fluidity and thickness of the membrane. A basic understanding of how physical mechanisms can regulate cell selectivity and resistance towards AMPs will aid in the development of new antimicrobial agents.

Platelet-Rich Fibrin Combined With a Porous Hydroxyapatite Graft for the Treatment of 3-Wall Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical Trial.

BACKGROUND: Porous hydroxyapatite (HA) bone grafting material has been used to fill periodontal intrabony defects (IBDs), resulting in clinically acceptable responses. Platelet-rich fibrin (PRF) is a leukocyte and platelet preparation that concentrates various polypeptide growth factors and, therefore, has the potential for use as regenerative treatment for periodontal defects. The present study aims to explore the clinical and radiographic effectiveness of autologous PRF versus PRF + HA in treatment of IBDs in patients with chronic periodontitis. METHODS: Ninety IBDs were treated with autologous PRF with open-flap debridement (OFD), PRF + HA with OFD, or OFD (controls) alone. Clinical and radiologic parameters, including probing depth (PD), clinical attachment level (CAL), IBD depth, and percentage defect fill were recorded at baseline and 9 months postoperatively. RESULTS: Mean PD reduction was greater in PRF (3.90 ± 1.09 mm) and PRF + HA (4.27 ± 0.98 mm) groups than the control group (2.97 ± 0.93 mm), and mean CAL gain was greater in PRF (3.03 ± 1.16 mm) and PRF + HA (3.67 ± 1.03 mm) compared to controls (2.67 ± 1.09 mm). Furthermore, significantly greater percentage of mean bone fill was found in the PRF (56.46% ± 9.26%) and PRF + HA (63.39% ± 16.52%) groups compared to controls (15.96% ± 13.91%). CONCLUSIONS: Treatment of IBD with PRF results in significant improvements of clinical parameters compared to baseline. When added to PRF, HA increases the regenerative effects observed with PRF in the treatment of 3-wall IBDs.

Autologous Platelet-Rich Fibrin in the Treatment of 3-Wall Intrabony Defects in Aggressive Periodontitis: A Randomized Controlled Clinical Trial.

BACKGROUND: Platelet-rich fibrin (PRF) has recently been applied in osseous regeneration. The aim of the present study is to explore the efficacy of PRF in treatment of intrabony defects (IBDs) in aggressive periodontitis. METHODS: Fifty-four IBDs in 17 patients were treated either with autologous PRF with open flap debridement (OFD) or OFD alone. Clinical and radiologic parameters such as probing depth (PD), clinical attachment level (CAL), IBD depth, and percentage defect change were recorded at baseline and 9 months postoperatively. RESULTS: Mean PD reduction and mean CAL gain were significantly greater in PRF compared with the control group. Furthermore, a significantly greater percentage of mean bone defect change was found in the PRF group. CONCLUSION: Within the limits of the present study, there is greater bone fill at sites treated with PRF with conventional OFD than conventional OFD alone.