Current Clinical Evidence Research Articles

Targeting the Renin-Angiotensin System (RAS) for Neuropsychiatric Disorders.

Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic targets. We aim to report current experimental and clinical evidence on the role of RAS in physiology and pathophysiology of mood disorders, schizophrenia, AD and related dementias. We also aim to discuss bottlenecks and future perspectives that can foster the development of new related therapeutic strategies. The available evidence supports positive therapeutic effects for neuropsychiatric disorders with the inhibition/antagonism of the ACE/Ang II/AT1 receptor axis or the activation of the ACE2/Ang-(1-7)/Mas receptor axis. Most of this evidence comes from pre-clinical studies and clinical studies lag much behind, hampering a potential translation into clinical practice.

A Review on the Extraction Process and Therapeutic Activity of Curcumin on Diabetes Mellitus and Cancer

Abstract: Turmeric or Curcuma Longa is a natural product whose medicinal properties have been widely studied and a wide range of therapeutic effects in various diseases, including neurodegenerative, liver, kidney damage, cancer and diabetes have been linked mainly to its curcuminoid content. In recent decades Diabetes has become an alarming global health problem due to the increasing prevalence of diabetes. The people who suffer from this disease and the consequences for them are devastating. In this review article we review the current basic and clinical evidence on the potential of curcumin / curcuminoids for the treatment of diabetes mainly due to its hypoglycemic, antioxidant and anti-inflammatory properties. Action of curcumin or curcuminoids as a hypoglycemic agent or only as a healing aid improve metabolic profile and improve diabetes-related complications such as diabetes nephropathy and cardiopathy are discussed. Interactions between curcumin and conventional antidiabetic drugs could be investigated in the treatment of diabetes Curcumin has also been shown to be a mediator of chemoresistance and radioresistance. Anticancer effects have been observed in a number of clinical trials, mainly a natural chemopreventive agent in colon and pancreatic cancer, cervical neoplasia and Barrett's metaplasia. Something clinical studies in healthy volunteers have shown low bioavailability of curcumin, calling into question the use of curcumin alone food additive Our clinical experience with curcumin and the antimetabolite gemcitabine in patients with advanced pancreatic cancer resulted in an objective response in less than 10% of patients with a small effect on survival. However, the safety of this combination has been proven. The potent antiproliferative effects of curcumin, which interact with multiple intracellular signaling pathways, may enhance the antitumor effects of gemcitabine. The Preclinical data lead to various, but still few, clinical trials (some ongoing) that demonstrated the potential effectiveness of the drug. this treatment as a chemopreventive or chemotherapeutic agent. This review focuses on clinical evidence including our experience with curcumin as a chemopreventive and therapeutic agent and background results in vitro.

The Importance of Optimal Thermal Ablation Margins in Colorectal Liver Metastases: A Systematic Review and Meta-Analysis of 21 Studies.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the US. Thermal ablation (TA) can be a comparable alternative to partial hepatectomy for selected cases when eradication of all visible tumor with an ablative margin of greater than 5 mm is achieved. This systematic review and meta-analysis aimed to encapsulate the current clinical evidence concerning the optimal TA margin for local cure in patients with colorectal liver metastases (CLM). MEDLINE, EMBASE, and the CENTRAL databases were systematically searched from inception until 1 May 2023, in accordance with the PRISMA Guidelines. Measure of effect included the risk ratio (RR) with 95% confidence interval (CI) using the random-effects model. Overall, 21 studies were included, comprising 2005 participants and 2873 ablated CLMs. TA with margins less than 5 mm were associated with a 3.6 times higher risk for LTP (n = 21 studies, RR: 3.60; 95% CI: 2.58-5.03; p-value < 0.001). When margins less than 5 mm were additionally confirmed by using 3D software, a 5.1 times higher risk for LTP (n = 4 studies, RR: 5.10; 95% CI: 1.45-17.90; p-value < 0.001) was recorded. Moreover, a thermal ablation margin of less than 10 mm but over 5 mm remained significantly associated with 3.64 times higher risk for LTP vs. minimal margin larger than 10 mm (n = 7 studies, RR: 3.64; 95% CI: 1.31-10.10; p-value < 0.001). This meta-analysis solidifies that a minimal ablation margin over 5 mm is the minimum critical endpoint required, whereas a minimal margin of at least 10 mm yields optimal local tumor control after TA of CLMs.

Psychotropics: A scientific, regulatory, and public view on the medicinal uses of cannabinoids and psilocybin

Research on psychotropics is gaining more popularity worldwide and support from drug regulatory agencies, which recognise the unmet medical needs of certain patient communities, such as patients with mental disorders and patients with cancer who experience depression. Cannabinoids and psilocybin have shown promising results in preclinical studies and clinical trials, but the current clinical evidence is scarce, and the regulatory requirements are strict due to high potential for drug abuse. The US FDA has recently released a draft, non-binding guidance on clinical trials with psychedelics. Europe is currently falling behind the US and Canada in terms of regulating psychotropic substances. The article provides a general introduction on conducting clinical trials with psychotropics and the regulatory requirements (as of October 2023) when submitting marketing authorisation application. In the near future, as more data becomes available, research on psychotropics will definitely shape the European regulatory landscape.

Diffusion kurtosis imaging and standard diffusion imaging in the magnetic resonance imaging assessment of prostate cancer.

In recent years, magnetic resonance imaging (MRI) has shown excellent results in the study of the prostate gland. MRI has indeed shown to be advantageous in the prostate cancer (PCa) detection, as in guiding targeting biopsy, improving its diagnostic yield. Although current acquisition protocols provide for multiparametric acquisition, recent evidence has shown that biparametric protocols can be non-inferior in PCa detection. Diffusion-weighted imaging (DWI) sequence, in particular, plays a key role, particularly in the peripheral zone which accounts for the larger part of the prostate. High b-values are generally recommended, although with the possibility of obtaining non-Gaussian diffusion effects, which requires a more sophisticated model for the analysis, namely through the diffusion kurtosis imaging (DKI). Purpose of this narrative review was to analyze the current applications and clinical evidence regarding the use of DKI with a main focus on PCa detection, also in comparison with DWI. This narrative review synthesized the findings of literature retrieved from main researches, narrative and systematic reviews, and meta-analyses obtained from PubMed. DKI analyses the non-Gaussian water diffusivity and describe the effect of signal intensity decay related to high b-value through two main metrics (Dapp and Kapp). Differently from DWI-apparent diffusion coefficient (DWI-ADC) which reflects only water restriction outside of cells, DKI metrics are supposed to represent also the direct interaction of water molecules with cell membranes and intracellular compounds. This review describes current evidence on ADC and DKI metrics in clinical imaging, and finally collect the results derived from the main articles focused on DWI and DKI models in detecting PCa. DKI advantages, compared to conventional ADC analysis, still remain controversial. Wider application and greater technical knowledge of DKI, however, may help in proving its intrinsic validity in the field of oncology and therefore in the study of clinically significant PCa. Finally, a deep understanding of DKI is important for radiologists to better understand what Kapp and Dapp mean in the context of different cancer and how these metrics may vary specifically in PCa imaging.

Siwak as a Prophetic and Evidence-Based Oral Hygiene Tool: A Qualitative Study among Islamic Scholars

Oral hygiene care and practice, siwak, which adopts Prophet Muhammad’s (Peace be upon Him, hereafter, PBUH) sunnah, remains unclear. As such, this study aims to explore and critically appraise the Prophetic practice of siwak according to Islamic literature, and in the light of current clinical evidence to clarify siwak as the oral hygiene practice prescribed by the Prophet (PBUH). Semi-structured one-to-one interviews was conducted among local contemporary Islamic scholars. The questions prepared were based on literature review and focused on toothcleaning practices of the Prophet (PBUH) as well as how the siwak was prepared and kept, as reported in documented narrations. Interview transcripts were analysed using thematic approach while content analysis of the referred narrations of hadith was made to provide a triangulation of the overall siwak use framework. The investigation revealed that horizontal tooth-brushing was highly recommended, and that al-Arak tree sticks are preferred to be 1) specifically prepared, 2) held steadily in the right hand, 3) used between two to five minutes depending on the goal, and 4) hygienically stored. It was also found that improper siwak practice may significantly suppress the clinical advantages. Thus, these findings substantiate future evidence-based guidelines on optimal oral hygiene care for siwak user based on authentic Islamic source.

The high-density lipoprotein: Attribute matters rather than amount in therapeutic arena

The ability of high-density lipoprotein (HDL-C) to absorb and recycle excess cholesterol from peripheral tissues back to the liver is particularly interesting. This ability may play a role in preventing atherosclerotic cardiovascular diseases, myocardial infarction, transient ischemic attack, and stroke. Prior epidemiological research has demonstrated that lower HDL-C concentration can be utilized to predict risk and has an inverse relationship with the risk of CVD. Elevated HDL-C levels are a hallmark of certain hereditary illnesses. However, this does not modulate to a lower risk of CVD. Researchers' focus has been diverted towards the shape and functions of the HDL molecule and its subclasses to correlate the possible causative association between HDL-C and adverse outcomes. Although a low level of HDL-C is a useful clinical predictor of CAD, raising the HDL-C level does not necessarily lower this risk. The possibility that HDL can either become less effective as an antioxidant or paradoxically enhance the oxidation and inflammation linked to atherosclerotic plaque under certain conditions contributes to the explanation of this dilemma. Thus, the functional properties of HDL, not merely the level, may need to be considered and developed. On the other hand, the available data indicates that higher HDL-C is not necessarily protective against cardiovascular disease. Conversely, it can be detrimental at extremely high levels. The objective of this review is to elucidate and discuss concisely the current clinical and scientific evidence related to the significance of HDL functionality over the biochemical HDL-C level in mediating the favorable effects on the cardiovascular system.

Effects of intramedullary nailing and internal fixation plates on postoperative wound infection and pain in patients with distal tibia fractures: A meta-analysis.

A meta-analysis was performed to assess the effects of intramedullary nailing (IMN) and internal fixation plates (IFP) on postoperative wound infection and pain in patients with distal tibia fractures, to provide evidence for the selection of surgical options for this group of patients. Computerised searches were performed on PubMed, Cochrane Library, EMBASE, MEDLINE, CNKI and Wanfang databases from the inception of each library to August 2023. All published randomised controlled trials (RCTs) comparing IMN with IFP for the treatment of patients with distal tibial fractures were selected. Literature screening, data extraction and literature evaluation were independently completed by two researchers. Data analysis was performed using the Review Manager 5.4 software. Overall, 25 RCTs with a total of 2011 patients were finally included, comprised by 1009 patients in the IMN group and 1002 patients in the IFP group. The rate of wound infection was significantly lower in the IMN group than that in the IFP group (5.05% vs. 9.58%, odds ratio [OR]: 0.52, 95% confidence intervals [CIs]: 0.37-0.73, p < 0.001). Meanwhile, the IMN group had a significantly higher rate of joint pain than that of the IFP group (14.57% vs. 2.90%, OR: 4.93, 95% CIs: 3.02-8.03, p < 0.00001), whereas the difference between the two surgical procedures in terms of operative time was not statistically significant (standardised mean differences: 0.08 95% CIs: -0.58-0.74, p = 0.82). Current clinical evidence suggests that both IMN and IFP are excellent treatments for distal tibial fractures. Although IMN is better in reducing postoperative wound infection, the risk of postoperative pain is higher. Thus, an appropriate surgical procedure should be selected in clinical practice in accordance with the actual situation of the patient, and IFP is used to reduce the incidence of postoperative joint pain when the anterior tibial soft tissue of the distal tibial fracture is in good condition, and vice versa. IMN is used to reduce the risk of infection.

Eradicating Atherosclerotic Events by Targeting Early Subclinical Disease: It Is Time to Retire the Therapeutic Paradigm of Too Much, Too Late.

Recent decades have seen spectacular advances in understanding and managing atherosclerotic cardiovascular disease, but paradoxically, clinical progress has stalled. Residual risk of atherosclerotic cardiovascular disease events is particularly vexing, given recognized lifestyle interventions and powerful modern medications. Why? Atherosclerosis begins early in life, yet clinical trials and mechanistic studies often emphasize terminal, end-stage plaques, meaning on the verge of causing heart attacks and strokes. Thus, current clinical evidence drives us to emphasize aggressive treatments that are delayed until patients already have advanced arterial disease. I call this paradigm "too much, too late." This brief review covers exciting efforts that focus on preventing, or finding and treating, arterial disease before its end-stage. Also included are specific proposals to establish a new evidence base that could justify intensive short-term interventions (induction-phase therapy) to treat subclinical plaques that are early enough perhaps to heal. If we can establish that such plaques are actionable, then broad screening to find them in early midlife individuals would become imperative-and achievable. You have a lump in your coronaries! can motivate patients and clinicians. We must stop thinking of a heart attack as a disease. The real disease is atherosclerosis. In my opinion, an atherosclerotic heart attack is a medical failure. It is a manifestation of longstanding arterial disease that we had allowed to progress to its end-stage, despite knowing that atherosclerosis begins early in life and despite the availability of remarkably safe and highly effective therapies. The field needs a transformational advance to shift the paradigm out of end-stage management and into early interventions that hold the possibility of eradicating the clinical burden of atherosclerotic cardiovascular disease, currently the biggest killer in the world. We urgently need a new evidence base to redirect our main focus from terminal, end-stage atherosclerosis to earlier, and likely reversible, human arterial disease.

How inhaled corticosteroids target inflammation in COPD.

Inhaled corticosteroids (ICS) are the most commonly used anti-inflammatory drugs for the treatment of COPD. COPD has been previously described as a "corticosteroid-resistant" condition, but current clinical trial evidence shows that selected COPD patients, namely those with increased exacerbation risk plus higher blood eosinophil count (BEC), can benefit from ICS treatment. This review describes the components of inflammation modulated by ICS in COPD and the reasons for the variation in response to ICS between individuals. There are corticosteroid-insensitive inflammatory pathways in COPD, such as bacteria-induced macrophage interleukin-8 production and resultant neutrophil recruitment, but also corticosteroid-sensitive pathways including the reduction of type 2 markers and mast cell numbers. The review also describes the mechanisms whereby ICS can skew the lung microbiome, with reduced diversity and increased relative abundance, towards an excess of proteobacteria. BEC is a biomarker used to enable the selective use of ICS in COPD, but the clinical outcome in an individual is decided by a complex interacting network involving the microbiome and airway inflammation.

Effect of short-term compression therapy after thermal ablation for varicose veins: study protocol for a prospective, multicenter, non-inferiority, randomized controlled trial

BackgroundFor patients with varicose veins, the goal is to relieve pain and swelling, reduce the severity of edema, improve skin changes, and heal ulcers associated with venous disease. Compression therapy is the cornerstone of their management. Several studies have shown that wearing an elastic bandage for the first 24 h and then a compression stocking for a week can effectively reduce the pain after thermal ablation. However, in clinical practice, patient compliance with this treatment could be better, considering difficulties in pulling up and removing the compression stocking, tightness, and skin irritation because these must be worn for a prolonged period. A potential solution to battling these barriers is short-term compression therapy. Besides, the effect and necessity of wearing compression stockings after thermal ablation have been questioned. Based on current clinical experience and limited evidence, although some scholars have suggested that compression therapy may be an unnecessary adjunctive therapy after thermal ablation, there is still a great deal of uncertainty in the absence of compression therapy after thermal ablation compared to compression therapy. Therefore, we advocate further research to evaluate the clinical effect of short-term postoperative compression therapy. Furthermore, well-designed randomized controlled trials are needed.MethodsA prospective, multicenter, non-inferiority randomized controlled trial is designed to evaluate the non-inferiority of target vein occlusion rate at 3 months. Three hundred and sixty patients will be randomly assigned in a 1:1 ratio to one of the following treatments: (A) 3 M™ Coban™ elastic bandage for 48 h or (B) 3 M™ Coban™ elastic bandage for the first 24 h and then a class II compression full-length stocking (23–32 mm Hg) for 1 week. The two groups will be compared on several variables, including target vein occlusion rate at 3 months (primary outcome indicator), pain, quality of life, clinical severity of varicose veins, postoperative complications, time to return to regular work, and compliance.DiscussionSuppose the effect of the 3 M™ Coban™ elastic bandage for 48 h proves to be non-inferior to long-term compression therapy. In that case, this short-term treatment may contribute to a future update of clinical guidelines for compression therapy after thermal ablation of varicose veins, resulting in higher patient compliance and better postoperative quality of life.Trial registrationClinical Trials NCT05840991. Registered on May 2023.

PCSK9 Targeting in the Management of Hypercholesterolaemia

It has long been established that elevated plasma concentrations of low-density lipoprotein cholesterol (LDL-C) are among the prominent contributors leading to the development of atherosclerotic plaques and, ultimately, cardiovascular disease. In the current era of optimal risk factor modification, proprotein convertase subtilisin/kexin type 9 (PCSK9) targeting has emerged as a potent therapeutic approach in the management of hypercholesterolaemia, addressing several substantial, unmet clinical needs. PCSK9 monoclonal antibodies, evolocumab and alirocumab, as well as inclisiran, which is a small interfering RNA that halts the transcription of PCSK9 mRNA, are being increasingly used in current clinical practice, as they induce intensive LDL-C reductions without any significant safety and tolerability concerns. Based on the success of these agents, the concept of PCSK9 targeting with novel agents with enhanced biological properties, or via different administration routes, has received considerable attention. In this regard, numerous antisense oligonucleotides, peptides, and proteins are currently under evaluation in randomised controlled trials, yielding propitious results up to date; they may enter clinical use in the coming years. Meanwhile, a PCSK9 vaccine, as well as genome editing via clustered regularly interspaced palindromic repeats/Cas9, hold great promise to eradicate LDL-C altogether as a cardiovascular risk factor. This review aims to present and discuss the current clinical and scientific evidence pertaining to the field of medications that exert their biological effect by targeting PCSK9, which are either in use in clinical practice, or are currently being evaluated in pre-clinical or clinical studies, and may prove beneficial in the near future.

The Potential of Scopolamine as an Antidepressant in Major Depressive Disorder: A Systematic Review of Randomized Controlled Trials.

Major depressive disorder is one of the most severe mental disorders. It strongly impairs daily functioning, and, in extreme cases, it can lead to suicide. Although different treatment options are available for patients with depression, there is an ongoing search for novel therapeutic agents, such as scopolamine (also known as hyoscine), that would offer higher efficacy, a more rapid onset of action, and a more favorable safety profile. The aim of our study was to review the current clinical evidence regarding the use of scopolamine, a promising therapeutic option in the treatment of depression. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases up to 5 June 2023. We included randomized placebo-controlled or head-to-head clinical trials that compared the clinical efficacy and safety of scopolamine in the treatment of major depressive disorder. Two reviewers independently conducted the search and study selection and rated the risk of bias for each study. Four randomized controlled trials were identified in the systematic review. The included studies investigated the use of scopolamine administered as an oral, intramuscular, or intravenous drug, alone or in combination with other antidepressants. The results indicated that scopolamine exerts antidepressant effects of varying intensity. We show that not all studies confirmed a statistically and clinically significant reduction of depressive symptoms vs. placebo. A broader perspective on scopolamine use in antidepressant treatment should be confirmed in subsequent large randomized controlled trials assessing both effectiveness and safety. Therefore, studies directly comparing the effectiveness of scopolamine depending on the route of administration are required.

Cochlear Implants for Children with Unilateral Hearing Loss: Debunking the Myths

Cochlear implants (CIs) have revolutionized the field of audiology, providing a life-changing solution for children with bilateral profound hearing loss. Expanding criteria has allowed children with significant unilateral hearing loss (UHL) to benefit from this technology as well. The practice is not without controversy, however. While we have known since 1984 that children with UHL face educational challenges (Bess &amp; Tharpe, 1984, 1986), watchful waiting until a child is old enough to be fitted with a Contralateral Routing of Signal (CROS) device has been the status quo (Bagatto, 2020; Bagatto et al., 2019). While research has continued to establish the benefits of cochlear implantation in this population, it has yet to become the standard of care. As is inherent in controversial practices, several myths and misconceptions surrounding the use of CIs for children with UHL pervade clinical hearing care systems. Here, we will debunk these myths by examining the evidence-based benefits and considerations associated with cochlear implantation in children with UHL. Through an analysis of current research and clinical evidence, we will highlight the potential advantages of CIs as a viable treatment option, promoting informed decision-making and improving the quality of life for children with UHL.

Ketorolac and bone healing: a review of the basic science and clinical literature.

Although the efficacy of ketorolac in pain management and the short duration of use align well with current clinical practice guidelines, few studies have specifically evaluated the impact of ketorolac on bony union after fracture or surgery. The purpose of this study was to review the current basic science and clinical literature on the use of ketorolac for pain management after fracture and surgery and the subsequent risk of delayed union or nonunion. Animal studies demonstrate a dose-dependent risk of delayed union in rodents treated with high doses of ketorolac for 4weeks or greater; however, with treatment for 7days or low doses, there is no evidence of risk of delayed union or nonunion. Current clinical evidence has also shown a dose-dependent increased risk of pseudoarthrosis and nonunion after post-operative ketorolac administration in orthopedic spine surgery. However, other orthopedic subspecialities have not demonstrated increased risk of delayed union or nonunion with the use of peri-operative ketorolac administration. While evidence exists that long-term ketorolac use may represent risks with regard to fracture healing, insufficient evidence currently exists to recommend against short-term ketorolac use that is limited to the peri-operative period. LEVEL OF EVIDENCE V: Narrative Review.

Application of next-generation imaging in biochemically recurrent prostate cancer.

Biochemical recurrence (BCR) following primary interventional treatment occurs in approximately one-third of patients with prostate cancer (PCa). Next-generation imaging (NGI) can identify local and metastatic recurrence with greater sensitivity than conventional imaging, potentially allowing for more effective interventions. This narrative review examines the current clinical evidence on the utility of NGI for patients with BCR. A search of PubMed was conducted to identify relevant publications on NGI applied to BCR. Given other relevant recent reviews on the topic, this review focused on papers published between January 2018 to May 2023. NGI technologies, including positron emission tomography (PET) radiotracers and multiparametric magnetic resonance imaging, have demonstrated increased sensitivity and selectivity for diagnosing BCR at prostate-specific antigen (PSA) concentrations <2.0 ng/ml. Detection rates range between 46% and 50%, with decreasing PSA levels for choline (1-3 ng/ml), fluciclovine (0.5-1 ng/ml), and prostate-specific membrane antigen (0.2-0.49 ng/ml) PET radiotracers. Expert working groups and European and US medical societies recommend NGI for patients with BCR. Available data support the improved detection performance and selectivity of NGI modalities versus conventional imaging techniques; however, limited clinical evidence exists demonstrating the application of NGI to treatment decision-making and its impact on patient outcomes. The emergence of NGI and displacement of conventional imaging may require a reexamination of the current definitions of BCR, altering our understanding of early recurrence. Redefining the BCR disease state by formalizing the role of NGI in patient management decisions will facilitate greater alignment across research efforts and better reflect the published literature.

Use of Tethers for Proximal Junctional Kyphosis Prophylaxis in Adult Spinal Deformity Surgery: A Review of Current Clinical Evidence.

Surgery for adult spinal deformity (ASD) often involves long-segment posterior instrumentation that introduces stress at the proximal junction that can result in proximal junctional kyphosis (PJK) or proximal junctional failure (PJF). Recently, the use of tethers at the proximal junction has been proposed as a means of buffering the transitional stresses and reducing the risk of PJK/PJF. Our objectives are to summarize the clinical literature on proximal junctional tethers for PJK/PJF prophylaxis. Articles published between 1 January 2000 and 10 November 2022 were identified via a PubMed search using combinations of the search terms "spine surgery," "ASD," "complication," "surgery," "PJK," "PJF," "tether," "sublaminar band," and "prophylaxis." No restrictions were placed on the number of patients, surgical indications, or surgical procedures. Relevant articles were reviewed and summarized. Fifteen articles were identified, including 2 prospective cohorts (Level II), 10 retrospective cohorts (Level III), and 3 retrospective case series (Level IV). All studies were published between 2016 and 2022, and all focused on ASD patient populations. The mean age in each study ranged from 55 to 69 years, and most studies had a mean follow-up of at least 12 months (range, 5.5-45.4 months). Eleven studies used a polyethylene tether, 2 used soft sublaminar cables, and 2 used semitendinous allograft. The tether extended to the UIV+1 or UIV+2, passing either through or around the spinous processes, in 13 studies. In the remaining 2 studies, the tether was passed sublaminar at the UIV+1. Fourteen studies favored the use of tethers with regard to reduction of PJK/PJF rates, and one demonstrated similar rates of PJK between the tether and no-tether groups. PJK/PJF remain major challenges in ASD surgery. Most early studies suggest that the use of tethers for ligamentous augmentation may help to mitigate the development of PJK/PJF. However, the multifactorial etiology of PJK/PJF makes it unlikely that any single technique will solve this complex problem. Further study is needed to address not only the effectiveness of junctional tethers but also to clarify whether there are optimal tether configurations, tether materials, and tether tension. 3.

Combining stereotactic body radiotherapy with immunotherapy in stage IV non-small cell lung cancer.

Immunotherapy has revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC). Oligometastasis has been associated with better prognosis than widespread metastatic disease and may be curable by stereotactic body radiotherapy (SBRT). SBRT can stimulate immunogenic anti-tumor activity, which can be further augmented when combined with immunotherapy, such as immune checkpoint inhibitors (ICIs). Thus, its combination with immunotherapy was recognized as a promising treatment option, especially in the metastatic setting. However, the most optimal approach to combine SBRT with immunotherapy remains controversial with early clinical evidence emerging. Here, we review the current clinical evidence supporting the combination of SBRT with immunotherapy in the treatment of metastatic NSCLC. Also, we discuss the current controversies and areas for further exploration associated with this treatment strategy.

Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by unexplained distressing pruritus in the mother and poses significant risk to the fetus of perinatal mortality. Occurring in the second and third trimester, the serum bile acid and aminotransferase are usually elevated in ICP patients. Ursodeoxycholic acid (UDCA) is the first line drug for ICP but the effectiveness for hepatoprotection is to a certain extent. In ICP patients with severe liver damage, combination use of hepatoprotective agents with UDCA is not uncommon. Herein, we reviewed the current clinical evidence on application of hepatoprotective agents in ICP patients. The underlying physiological mechanisms and their therapeutic effect in clinical practice are summarized. The basic pharmacologic functions of these hepatoprotective medications include detoxification, anti-inflammation, antioxidation and hepatocyte membrane protection. These hepatoprotective agents have versatile therapeutic effects including anti-inflammation, antioxidative stress, elimination of free radicals, anti-steatohepatitis, anti-fibrosis and anti-cirrhosis. They are widely used in hepatitis, non-alcoholic fatty liver disease, drug induced liver injury and cholestasis. Evidence from limited clinical data in ICP patients demonstrate reliable effectiveness and safety of these medications. Currently there is still no consensus on the application of hepatoprotective agents in ICP pregnancies. Dynamic monitoring of liver biochemical parameters and fetal condition is still the key recommendation in the management of ICP pregnancies.

Acquired Hemophilia A after SARS-CoV-2 Infection: A Case Report and an Updated Systematic Review.

The role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been implicated in the pathogenesis of acquired hemophilia A (AHA). The aim of this study is to report our case and to summarize clinical studies on de novo AHA after SARS-CoV-2 infection. We performed a systematic search on the association of SARS-CoV-2 with AHA in four medical databases up to 28 May 2023. Eligible studies should include de novo AHA patients who had SARS-CoV-2 infection before or concomitant with the diagnosis of AHA. Findings were synthesized narratively. In addition, we report the case of a 62-year-old female patient, who presented to our clinic with left flank pain 2 weeks after SARS-CoV-2 infection. Clinical investigations confirmed AHA and imaging studies revealed retroperitoneal bleeding. Her hemostasis was successfully secured with bypassing agents; however, despite immunosuppressive therapy, high inhibitor titer persisted. In the systematic review, we identified only 12 relevant cases with a questionable cause-effect relationship between SARS-CoV-2 infection and AHA. Based on the qualitative analysis of the relevant publications, current clinical evidence is insufficient to support a cause-effect relationship. The analysis of data from ongoing AHA registries can serve further evidence.