Serum lactate dehydrogenase and its isoenzymes as predictors of clinical outcomes in acute exacerbation of chronic obstructive pulmonary disease: a retrospective analysis of a hospitalized cohort.

We aimed to test the association between serum lactate dehydrogenase (LDH) and its isoenzymes and treatment outcomes during hospitalization for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Thirty-eight AECOPD patients were recruited from a tertiary hospital from December 2017 to June 2018. Serum LDH and LDH isoenzymes were measured on venous blood collected at admission. Treatment outcomes included duration of hospital stay, initiation of non-invasive (NIV) or mechanical ventilation, initiation of antipseudomonal antibiotics, change in empirical antibiotic treatment, need for intravenous corticosteroids or methylxanthines, and percentage of change in C-reactive protein from admission to the third day. Multivariate linear and binary logistic regression analyses were used to test the study's objectives. We found that, after adjusting for age, gender, comorbidities, COPD severity, level of hypoxemia, and inflammation markers, each 10 U/L increase in serum LDH was associated with prolongation of the hospital stay by 0.25 (0.03, 0.46) days, 42% higher odds (odds ratio [OR] 1.42 [1.00, 2.03]) for need of NIV, and 25% higher odds (OR 1.25 [1.04, 1.49]) for initiation of antipseudomonal treatment. LDH1 and LDH2 were the LDH isoenzymes that mainly drove these relationships. LDH release in the context of an AECOPD could originate from lung, muscle, or heart tissue damage due to airway inflammation, respiratory muscle recruitment, and myocardial stress. Myocardial injury and aerobic adaptation in respiratory muscles may explain the predominance of LDH1 and LDH2 isoenzymes in these associations.

Cytomegalovirus pneumonia in an immunocompetent host with primary ciliary dyskinesia: A case report.

Primary ciliary dyskinesia (PCD) is an autosomal-recessive inherited disease caused by mutations in genes involved in ciliary structure and function leading to impaired mucociliary clearance and repeated or chronic, usually bacterial, infections of the upper and lower airways and decreased lung function and bronchiectasis. Cytomegalovirus (CMV) is a DNA virus that usually causes subclinical infection and in 10% of the patients causes a mononucleosis-like syndrome. CMV is a causative agent of serious illness in vulnerable immunocompromised groups such as transplant recipients, patients with immunodeficiency or malignancy and neonates. Life-threatening infection due to CMV, including CMV pneumonia, is not common in immunocompetent patients. In this report we describe a case of an otherwise immunocompetent woman, suffering from PCD, who developed severe CMV pneumonia.

Pulmonary adverse events due to immune checkpoint inhibitors: A literature review.

Cancer immunotherapy aims to stimulate the immune system to fight against tumors, utilizing the presentation of molecules on the surface of the malignant cells that can be recognized by the antibodies of the immune system. Immune checkpoint inhibitors, a type of cancer immunotherapy, are broadly used in different types of cancer, improving patients' survival and quality of life. However, treatment with these agents causes immune-related toxicities affecting many organs. The most frequent pulmonary adverse event is pneumonitis representing a non-infective inflammation localized to the interstitium and alveoli. Other lung toxicities include airway disease, pulmonary vasculitis, sarcoid-like reactions, infections, pleural effusions, pulmonary nodules, diaphragm myositis and allergic bronchopulmonary aspergillosis. This review aims to summarize these pulmonary adverse events, underlining the significance of an optimal expeditious diagnosis and management.

Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice.

BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction (NMJ), mostly associated with acetylcholine receptor (AChR) antibodies. Around 5-10 % of MG patients show antibodies to muscle-specific tyrosine kinase (MuSK). Mesenchymal stem cell (MSC) administration has been shown to ameliorate muscle weakness in the experimental autoimmune myasthenia gravis (EAMG) model induced by AChR immunization. METHODS: To investigate the efficacy of stem cell treatment in MuSK-related EAMG, clinical and immunological features of MuSK-immunized mice with or without dental follicle MSC (DFMSC) treatment were compared. RESULTS: MuSK-immunized mice intravenously treated with DFMSC after second and third immunizations showed significantly lower EAMG incidence and severity and reduced serum anti-MuSK antibody, NMJ IgG, and C3 deposit levels and CD11b+ lymph node cell ratios. Moreover, lymph node cells of DFMSC-administered mice showed reduced proliferation and IL-6 and IL-12 production responses to MuSK stimulation. By contrast, proportions of B and T cell populations and production of a wide variety of cytokines were not affected from DFMSC treatment. CONCLUSIONS: Our results suggest that DFMSC treatment shows its beneficial effects mostly through suppression of innate immune system, whereas other immune functions appear to be preserved. Stem cell treatment might thus constitute a specific and effective treatment method in MuSK-associated MG.

Reduced muscle mitochondrial enzyme activity in MuSK-immunized mice.

AIM: Muscle specific kinase (MuSK) antibody-positive myasthenia gravis(MG) patients might present with clinical and electrophysiological signs of muscle atrophy. In this study, we investigated the potential contribution of mitochondrial dysfunction to muscle atrophy induced by MuSK immunity. METHODS: Mitochondrial enzyme expression was investigated in muscle samples of MuSK-immunized, acetylcholine receptor (AChR)-immunized, and complete Freund's adjuvant (CFA)-immunized C57BL/6 (B6) mice using histochemical methods. Mitochondrial enzyme activity was also investigated in MuSK- and CFA-immunized mice. RESULTS: Histochemical analysis showed normal muscle fiber activity on succinate dehydrogenase (SDH) and cytochrome oxidase (COX) stains in all immunization groups. However, MuSK-immunized mice had more ragged-red fibers on modified Gomori-trichrome (MGT) stain and more pronounced type 1 muscle fiber atrophy. MuSK-immunized mice also showed reduced citrate synthase, SDH, and NADH-cytochrome c-reductase activity. DISCUSSION: Our results suggest that MuSK-immunity might induce muscle atrophy through mitochondrial dysfunction.

T cell repertoire in DQ5-positive MuSK-positive myasthenia gravis patients.

Myasthenia gravis (MG) is a prototypical antibody-mediated disease characterized by muscle weakness and fatigability. Serum antibodies to the acetylcholine receptor and muscle-specific tyrosine kinase receptor (MuSK) are found in about 85% and 8% of patients respectively. We have previously shown that more than 70% of MG patients with MuSK antibodies share the HLA DQ5 allele. The aim of the present study was to analyze the T cell receptor (TCR) repertoire specific for recombinant human MuSK protein. We used the CDR3 TRBV-TRBJ spectratyping (immunoscope) to analyze the T cell response to MuSK from 13 DQ5+ MuSK-MG patients and from 7 controls (six DQ5+ MuSK negative subjects and one DQ5- DQ3+ MuSK positive patient). DQ5+ MuSK-MG patients but not controls used a restricted set of TCR VJ rearrangements in response to MuSK stimulation. One semiprivate (TRBV29-TRBJ2.5) rearrangement was found in 5/13 patients, while 4 other semiprivate (one in TRBV28-TRBJ2.1 and in TRBV3-TRBJ1.2, and two in TRBV28-TRBJ1.2) rearrangements were differently shared by 4/13 patients each and were absent in controls. When we sequenced the TRBV29-TRBJ2.5 rearrangement, we obtained 26 different sequences of the expected 130 bp length from 117 samples of the 5 positive patients: two common motifs GXGQET/TEHQET were shared in 4 patients as semiprivate motifs. Thus, the MuSK-specific T-cell response appears to be restricted in DQ5+ MuSK-MG patients, with a semiprivate repertoire including a common motif of TRBV29. This oligoclonal restriction of T cells will allow the identification of immunodominant epitopes in the antigen, providing therefore new tools for diagnosis and targeted therapy.

Malignant character of an ossified posterior longitudinal ligament in a hyperflexion injury: A case report.

The present study reports the case of a 50-year-old obese male with ankylosing spondylitis, Scheuermann's kyphosis. The patient was asymptomatic concerning the ectopic ossification of the posterior longitudinal ligament (OPLL) at the cervical spine; he developed quadriparesis and respiratory insufficiency following minor head trauma. Even though trauma to the cervical spine in patients with OPLL is common, to the best of our knowledge, this is the first reported case of an extensive osteophyte with a lethal outcome after syncope. In rare occasions, it may be present with syncope and potentially lethal outcomes, particularly when precipitated by trauma. Therefore, the management of OPLL with significant canal stenosis should not be unnecessarily delayed.

Association between polymorphisms of DNA repair genes and intracranial aneurysms: A systematic review and meta­analysis.

Intracranial aneurysms (IAs) are present in ~2% of the general population, and genetic factors cannot be excluded for the risk of their development. The gene factors that result in the changes in the vascular extracellular matrix (ECM) may also be a key reason for IAs being hereditary. The VCAN gene [also known as chondroitin sulfate proteoglycan 2 (CSPG2)] plays various roles in maintaining ECM functions. The present systematic review and meta-analysis aimed to investigate all eligible articles involving IAs on the association with germ line SNPs of DNA repair genes (up to January, 2024). The total number of patients was 2,308 [987 cases (poor outcomes) and 1,321 controls (good outcomes)]. The results revealed that rs2287926 G/G genotype and G allele and rs251124 T/T genotype and minor allele T increased the risk of developing IAs. However, further studies are required to examine these gene polymorphisms as screening markers for IAs.

Exploring the association between melatonin and nicotine dependence (Review).

Due to the addictive qualities of tobacco products and the compulsive craving and dependence associated with their use, nicotine dependence continues to be a serious public health concern on a global scale. Despite awareness of the associated health risks, nicotine addiction contributes to numerous acute and chronic medical conditions, including cardiovascular disease, respiratory disorders and cancer. The nocturnal secretion of pineal melatonin, known as the 'hormone of darkness', influences circadian rhythms and is implicated in addiction­related behaviors. Melatonin receptors are found throughout the brain, influencing dopaminergic neurotransmission and potentially attenuating nicotine­seeking behavior. Additionally, the antioxidant properties of melatonin may mitigate oxidative stress from chronic nicotine exposure, reducing cellular damage and lowering the risk of nicotine­related health issues. In addition to its effects on circadian rhythmicity, melatonin acting via specific neural receptors influences sleep and mood, and provides neuroprotection. Disruptions in melatonin signaling may contribute to sleep disturbances and mood disorders, highlighting the potential therapeutic role of melatonin in addiction and psychiatric conditions. Melatonin may influence neurotransmitter systems involved in addiction, such as the dopaminergic, glutamatergic, serotonergic and endogenous opioid systems. Preclinical studies suggest the potential of melatonin in modulating reward processing, attenuating drug­induced hyperactivity and reducing opioid withdrawal symptoms. Chronotherapeutic approaches targeting circadian rhythms and melatonin signaling show promise in smoking cessation interventions. Melatonin supplementation during periods of heightened nicotine cravings may alleviate withdrawal symptoms and reduce the reinforcing effects of nicotine. Further research is required however, to examine the molecular mechanisms underlying the melatonin­nicotine association and the optimization of therapeutic interventions. Challenges include variability in individual responses to melatonin, optimal dosing regimens and identifying biomarkers of treatment response. Understanding these complexities could lead to personalized treatment strategies and improve smoking cessation outcomes.

Surgical outcomes of patients with unruptured anterior vs. inferior circulation aneurysms: A meta­analysis.

The treatment option for unruptured intracranial aneurysms (UIAs) depends on their natural history-related risk of rupture vs. the risk of surgical management. The present meta-analysis sought to assess the association between the surgical outcomes of anterior and posterior circulation UIAs. The present study investigated the comparative articles involving the surgical treatment of anterior vs. posterior circulation UIAs through electronic databases, including the Cochrane Library, PubMed (1980 to March, 2023), Medline (1980 to March, 2023) and EMBASE (1980 to March, 2023). Quoting all exclusion and inclusion criteria, nine articles finally remained for statistical analysis. The entire number of patients included in these nine articles was 3,253 (2,662 in the anterior and 591 in the posterior circulation UIAs group). The present meta-analysis proposes that the surgical treatment of anterior circulation UIAs is associated with better outcomes compared with the surgical management of posterior circulation UIAs.

Exploring the pathogenetic mechanisms of Mycoplasmapneumoniae (Review).

Mycoplasmas, the smallest self-replicating prokaryotes without a cell wall, are the most prevalent and extensively studied species in humans. They significantly contribute to chronic respiratory tract illnesses and pneumonia, with children and adolescents being particularly vulnerable. Mycoplasma pneumoniae (M. pneumoniae) infections typically tend to be self-limiting and mild but can progress to severe or even life-threatening conditions in certain individuals. Extrapulmonary effects often occur without pneumonia, and both intrapulmonary and extrapulmonary complications operate through separate pathological mechanisms. The indirect immune-mediated damage of the immune system, vascular blockages brought on by vasculitis or thrombosis and direct harm from invasion or locally induced inflammatory cytokines are potential causes of extrapulmonary manifestations due to M. pneumoniae. Proteins associated with adhesion serve as the primary factor crucial for the pathogenicity of M. pneumoniae, relying on a specialized polarized terminal attachment organelle. The type and density of these host receptors significantly impact the adhesion and movement of M. pneumoniae, subsequently influencing the pathogenic mechanism and infection outcomes. Adjacent proteins are crucial for the proper assembly of the attachment organelle, with variations in the genetic domains of P1, P40 and P90 surfaces contributing to the variability of clinical symptoms and offering new avenues for developing vaccines against M. pneumoniae infections. M. pneumoniae causes oxidative stress within respiratory tract epithelial cells by adhering to host cells and releasing hydrogen peroxide and superoxide radicals. This oxidative stress enhances the vulnerability of host cells to harm induced by oxygen molecules. The lack of superoxide dismutase and catalase of bacteria allows it to hinder the catalase activity of the host cell, leading to the reduced breakdown of peroxides. Lung macrophages play a significant role in managing M. pneumoniae infection, identifying it via Toll-like receptor 2 and initiating the myeloid differentiation primary response gene 88-nuclear factor κΒ signaling cascade. However, the precise mechanisms enabling M. pneumoniae to evade intracellular host defenses remain unknown, necessitating further exploration of the pathways involved in intracellular survival. The present comprehensive review delves into the pathogenesis of M. pneumoniae infection within the pulmonary system and into extrapulmonary areas, outlining its impact.

Acute intracranial hemorrhage during the installation of the LICOX microdialysis system: A case report.

Neuro-monitoring is widely employed for the evaluation of intubated patients in the intensive care unit with stroke, severe head trauma, subarachnoid hemorrhage and/or hepatic encephalopathy. The present study reports the case of a patient with acute intracranial hemorrhage following the insertion of neuromonitoring catheters, which required surgical management. The patient was a 14-year-old male who sustained a severe traumatic brain injury and underwent a right-sided hemicraniectomy. During the installation of the neuromonitoring catheters, an acute hemorrhage was noted with a rapidly elevating intracranial pressure. A craniotomy was performed to identify and coagulate the injured cortical vessel. As demonstrated herein, the thorough evaluation of the clotting profile of the patient, a meticulous surgical technique and obtaining a post-insertion computed tomography scan may minimize the risk of any neuromonitoring-associated hemorrhagic complications.

Precision medicine for respiratory diseases: A current viewpoint.

In the realm of respiratory illnesses, despite the immense costs and efforts invested in diagnosis and treatment, numerous patients with chronic respiratory conditions or malignancies do not respond well to existing therapies. Delayed diagnoses and inadequate treatments contribute to these challenges, along with adverse reactions or treatment limitations due to side-effects. However, recent advancements in understanding respiratory diseases have paved the way for personalized medical treatments, considering individual genetic, molecular and environmental factors. Precision medicine, which accommodates individual differences in disease susceptibility and response to treatments, aims to improve patient care by aligning medical research with tailored therapies. Innovative technologies, such as genomic sequencing and biomarker identification contribute to this approach, allowing for customized treatments and the identification of effective therapies. Additionally, the application of precision medicine in lung cancer treatment exemplifies the forefront of individualized care within respiratory medicine. Several studies have explored the role of precision medicine in managing respiratory infectious diseases, asthma and idiopathic pulmonary fibrosis, aiming to categorize diseases more accurately and design targeted therapies. The ultimate goal is to enhance treatment effectiveness, minimize adverse events, and shift towards a patient-centered approach to managing respiratory conditions. Despite limitations, precision medicine holds promise for improving patient outcomes and emphasizing personalized care in respiratory medicine.

Management of intracranial cavernous malformations using conservative vs. surgical and/or radiosurgical treatment: A systematic review and meta­analysis.

Intracranial cavernous malformations (CMs) are vascular lesions with a high bleeding rate. At present, the debate regarding their treatment is still ongoing. The present systematic review and meta-analysis aimed to evaluate the safety of surgery or radiosurgery (SRS) for the management of CMs and to determine their potential outcomes compared with conservative treatment. The present systematic review and meta-analysis investigated the relative articles involving the management of intracranial CMs, namely their natural history (conservative treatment) vs. surgical/SRS treatment through electronic databases until June, 2023. The collected variables included the first author's name, the study period covered, the year of publication, the total number of patients examined and their age, and the number of males. In total, six articles met the eligibility criteria. The total number of patients was 399 (157 in the surgery/SRS group and 242 in the conservative treatment group). The results revealed that surgical or SRS management is a safe procedure for CMs compared with conservative treatment. Notably, the use of hemosiderin in the pre-MRI, the free of seizures parameter and the neurological deficit parameters were associated with improved outcomes in the surgical or SRS group of patients.

Comparison of surgical techniques for the treatment of chronic subdural hematomas: A single­center case series.

Chronic subdural hematoma (CSDH) is one of the most challenging realities in the neurosurgical world. The aim of the present study was to compare different surgical techniques, such as burr hole evacuation with subperiosteal drain or subdural drain and mini-craniotomy, and to review the diverse outcomes on the post-operative clinical state of patients. The present study was a retrospective cohort study with 122 patients with CSDH treated at a single center. The patients were separated into three groups according to the surgical technique used as follows: group 1, two burr holes with the placement of a subperiosteal drain; group 2, single burr hole per hematoma with the placement of an intradural drain; and group 3, mini-craniotomy. The duration of hospitalization, hematoma recurrence, complications, Glasgow coma scale at discharge and mortality were reported as outcome measures. A total of 3 patients succumbed following hematoma evacuation; of these 2 patients were from group 2 and 1 patient was from group 3. The patients from groups 1 and 3 exhibited a significantly lower odds ratio (OR) of hematoma recurrence than patients in group 2 (OR, 0.76; P<0.01; and OR, 0.8; P<0.01, respectively). The patients in group 1 exhibited a significantly lower probability of having a depressed level of consciousness on discharge (OR, 0.249; P=0.031). Group 2 was associated with a statistically significant prolongation of hospitalization. On the whole, the present study demonstrates that multiple burr hole hematoma evacuation with subperiosteal drain placement and mild suction is a very promising technique with very beneficial post-operative outcomes, such as zero mortality, a low CSDH recurrence risk, a reduced period of hospitalization and an improved post-operative quality of life.

Prevalence of ACA variations: A systematic review and meta­analysis.

The anterior cerebral artery (ACA) and its divisions enclose symptomatically critical and supplementary differentiations. Anatomical variations of the distal ACA that are irregularly detected can be separated into three major groups, namely, azygos, bihemispheric and median ACA variations. The present study performed a systematic review and meta-analysis. The PICOS criteria and electronic databases, namely the Cochrane Library, PubMed (until December, 2023), Embase (until December, 2023) and MEDLINE (until December, 2023) were used to identify 48 articles to fulfill the eligible criteria. As a limited number of studies exist on the prevalence of ACA anatomical variations, the present meta-analysis aimed to determine the precise incidence of these variants. In addition, with the comparative description between cadaveric (autopsy) and imaging cases, more accurate results were extract from the prevalence presentation of the distal ACA variants. On the whole, no statistically significant differences were found between autopsy and imaging studies.

Efficacy of decompressive craniectomy: A retrospective case series study with 321 patients and an update on controversies.

Decompressive craniectomy (DC) is considered a cornerstone in the management of refractory intracranial hypertension. For decades, DC was known as an occasionally lifesaving procedure; however, it was associated with numerous severe complications. The present study is a single-center retrospective case series study on with 321 patients who underwent DC between January, 2010 and December, 2020. All patients were divided into four groups as follows: Group A included patients who suffered from a space-occupying middle cerebral artery (MCA) ischemic event; group B included individuals who developed intracerebral hemorrhage; group C included patients admitted for traumatic brain injury; and group D included patients with other neurosurgical entities that underwent DC, such as subarachnoid hemorrhage, tumors, brain abscess and cerebral ventricular sinus thrombosis events. The present study enrolled a total of 321 patients who underwent DC. Group A included 52 out of the 321 (16.1%) patients, group B included 51 (15.8%) patients, group C included 164 (51.0%) patients, and group D included 54 (16.8%) patients. Of the 321 patients, 235 (73.2%) were males, and the median age was 53.7 years. Multivariate analysis revealed that only the group A parameter was an independent factor associated with a Glasgow outcome scale score >2 during follow-up (P<0.05). On the whole, the results of the present study suggest that among patients who underwent DC with different neurological entities, those who had experienced MCA events had more favorable outcomes.

Role of decompressive craniectomy in the management of acute ischemic stroke (Review).

The application of decompressive craniectomy (DC) is thoroughly documented in the management of brain edema, particularly following traumatic brain injury. However, an increasing amount of concern is developing among the universal medical community as regards the application of DC in the treatment of other causes of brain edema, such as subarachnoid hemorrhage, cerebral hemorrhage, sinus thrombosis and encephalitis. Managing stroke continues to remain challenging, and demands the aggressive and intensive consulting of a number of medical specialties. Middle cerebral artery (MCA) infarcts, which consist of 1-10% of all supratentorial infarcts, are often associated with mass effects, and high mortality and morbidity rates. Over the past three decades, a number of neurosurgical medical centers have reported their experience with the application of DC in the treatment of malignant MCA infarction with varying results. In addition, over the past decade, major efforts have been dedicated to multicenter randomized clinical trials. The present study reviews the pertinent literature to outline the use of DC in the management of malignant MCA infarction. The PubMed database was systematically searched for the following terms: 'Malignant cerebral infarction', 'surgery for stroke', 'DC for cerebral infarction', and all their combinations. Case reports were excluded from the review. The articles were categorized into a number of groups; the majority of these were human clinical studies, with a few animal experimental clinical studies. The surgical technique involved was DC, or hemicraniectomy. Other aspects that were included in the selection of articles were methodological characteristics and the number of patients. The multicenter randomized trials were promising. The mortality rate has unanimously decreased. As for the functional outcome, different scales were employed; the Glasgow Outcome Scale Extended was not sufficient; the Modified Rankin Scale and Bathel index, as well as other scales, were applied. Other aspects considered were demographics, statistics and the very interesting radiological ones. There is no doubt that DC decreases mortality rates, as shown in all clinical trials. Functional outcome appears to be the goal standard in modern-era neurosurgery, and quality of life should be further discussed among the medical community and with patient consent.

Comparison of surgical outcomes between primary and secondary brain abscess.

Brain abscess (BA) constitutes 1-8% of intra-cerebral tumors, and thus the present study aimed to compare the surgical outcomes of patients with primary and secondary BA. The present retrospective study examined 32 of cases BA who underwent surgery in a local institution between February, 2013 and December, 2023. All patients received intravenous antibiotic therapy according to the antibiogram for antimicrobial susceptibility. In total, 32 patients were separated into two groups as follows: Group A (16 patients, 50%) with primary abscess and group B (16 patients, 50%) with secondary abscess. Of the 32 patients included in the study, 23 (71.8%) were males, and the median age was 55.3 years. On the whole, the present study demonstrates that a multidisciplinary approach involving a combination of often multiple surgical procedures and prolonged antibiotic medication may improve the functional outcome if the underlying pathology allows for a functional outcome.

Bone graft absorption complication following cranioplasty: A retrospective institutional study.

The aim of the present retrospective study was to confer the factors that are related to bone graft absorption and affect the outcomes of patients following cranioplasty (CPL). The present retrospective study includes cases of patients that underwent CPL between February, 2013 and December, 2022. All participants had a follow-up period of 1 to 10 years from the day of discharge from the hospital. In total, 116 (62.3%) of the 186 patients that underwent decompressive craniectomy (DC) were enrolled in the present study for CPL. A total of 109 (93.9%) patients were included in group A, and 7 (6.0%) patients were included in group B. On the whole, the results of the present study suggest that a CPL after 2.5-7.7 months of DC increases the possibility of bone absorption.