Treatment Modalities Research Articles

Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy.

Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences. A cohort study spanning 10years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits. Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304days, IQR 1433-3274) indicated favorable outcomes in both groups. This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.

6622 Severe Primary Hypothyroidism in a Child Presented as a Pituitary Tumour; a case Report

Abstract Disclosure: S.S. Awadalla: None. A 9-year-old patient showed up to the emergency department due to a headache that had been going on for a month without other symptoms and no neurological alterations. Complete blood count and glycemia were normal. A Cerebral MRI was requested and showed a pituitary adenoma. The patient was initially evaluated by neurosurgeons and referred to a pediatric endocrinologist. TSH, free T4, IGFI, and cortisol were evaluated, TSH was found to be high at 936 (normal, 0.4-4.2), free T4 &amp;lt; 0.4; suggestive of severe primary hypothyroidism. The case was analysed with the neurosurgery department, and a joint decision to start therapy with LT4 was taken, whilst monitoring the evolution of the pituitary adenoma. TSH and Free T4 were normal, and the MRI of Sella Turcica three months later showed complete pituitary normality. The presentation of this case is of relevance as the primary modality of treatment is thyroid hormone supply and not surgery. Interprofessional team integration is recommended for the treatment of patients with this condition. Presentation: 6/1/2024

Latent space representation of electronic health records for clustering dialysis-associated kidney failure subtypes

ObjectiveKidney failure manifests in various forms, from sudden occurrences such as Acute Kidney Injury (AKI) to progressive like Chronic Kidney Disease (CKD). Given its intricate nature, marked by overlapping comorbidities and clinical similarities—including treatment modalities like dialysis—we sought to design and validate an end-to-end framework for clustering kidney failure subtypes. Materials and methodsOur emphasis was on dialysis, utilizing a comprehensive dataset from the UK Biobank (UKB). We transformed raw Electronic Health Record (EHR) data into standardized matrices that incorporate patient demographics, clinical visit data, and the innovative feature of visit time-gaps. This matrix structure was achieved using a unique data cutting method. Latent space transformation was facilitated using a convolution autoencoder (ConvAE) model, which was then subjected to clustering using Principal Component Analysis (PCA) and K-means algorithms. ResultsOur transformation model effectively reduced data dimensionality, thereby accelerating computational processes. The derived latent space demonstrated remarkable clustering capacities. Through cluster analysis, two distinct groups were identified: CKD-majority (cluster 1) and a mixed group of non-CKD and some CKD subtypes (cluster 0). Cluster 1 exhibited notably low survival probability, suggesting it predominantly represented severe CKD. In contrast, cluster 0, with substantially higher survival probability, likely to include milder CKD forms and severe AKI. Our end-to-end framework effectively differentiates kidney failure subtypes using the UKB dataset, offering potential for nuanced therapeutic interventions. ConclusionsThis innovative approach integrates diverse data sources, providing a holistic understanding of kidney failure, which is imperative for patient management and targeted therapeutic interventions.

6606 Connshing Syndrome: An Uncommon Presentation Of Bilateral Adrenal Mass

Abstract Disclosure: C.S. Botero Suarez: None. N. Meda: None. K. Lamar: None. S.K. Suryanarayanan: None. Introduction: Mild autonomous hypersecretion of cortisol in the underlying setting of hyperaldosteronism has been described before and coined the term Connshing Syndrome. Even though it was described in 1979, recently W. Arlt et al in 2017 revived interest in the topic of Connshing Syndrome represents a distinct entity among PA (primary hyperaldosteronisms). We present a case of bilateral adrenal mass associated with mild autonomous hypersecretion of cortisol as well as the development of primary aldosteronism. Case Description: A 62-year-old male with a medical history of hyperlipidemia, hypertension, spontaneous hypokalemia, and T2DM was referred to the clinic due to concerns for hyperaldosteronism. Exam was unremarkable for signs of hypercortisolism. Blood pressure in the clinic was 143/88 mmHg, pulse 81 bpm, weight 105.4 Kg (231.8 lbs.), and a BMI of 28 kg/m2. A non-contrast abdominal CT performed, showed a 2.9 x.1.4 cm right adrenal lipid-rich adenoma with -3.7 HU, as well as a left adrenal lipid-rich adenoma of 1.8 x 1.3 x cm and -7.7 HU. A hormonal workup showed normal plasma metanephrines, an aldosterone of 39 ng/dL, plasma renin activity 0.16 ng/mL/h, and aldosterone/PRA ratio of 243. The patient underwent 1 mg dexamethasone suppression test which resulted in an ACTH &amp;lt;5 pg/mL, dexamethasone level of 288 ng/dL, and cortisol of 1.9 mcg/dL. AVS with Cosyntropin was performed (see Table 1). Right sided adrenalectomy is being considered but the identification of possible lateralization of cortisol is being considered. Discussion: Surgical management is usually preferred treatment modality for both unilateral PA and MACS, but identification of lateralization of both cortisol and aldosterone can be difficult. Although identifying lateralization of aldosterone with Cosyntropin-stimulated AVS is well understood, lateralization of cortisol production is not well understood. Johnson et. all have suggested the use of adrenal venous sampling with dexamethasone suppression as well as measurement of epinephrine levels to identify the source of hypercortisolism. They demonstrated identification of cortisol lateralization with adrenal vein sampling with specificity of 95 – 100% for unilateral disease utilizing a AV/IVC cortisol ratio &amp;gt; 9 and a cortisol lateralization ratio (CLR) of &amp;gt; 2.3. Although our case had a Cosyntropin-stimulated AVS showing clear lateralization of aldosterone production to the right adrenal, the lateralization of cortisol production is yet unknown and AVS with dexamethasone suppression is being considered. Although the treatment considerations are traditionally utilizing the guidelines for both PA and Cushing Syndrome guidelines respectively, very little is known when there are divergence of autonomous secretion amongst the bilateral adrenal masses and more studies are needed to clarify the long-term treatment considerations. 1 Presentation: 6/3/2024

7437 Harnessing Diabetes Technology for Management of Immune Checkpoint Inhibitor Associated Diabetes

Abstract Disclosure: A. Knape: None. A. Kotwal: None. D. Rohlfsen: None. A. Patel: None. W. Goldner: None. Background: Immune checkpoint inhibitors (ICIs) are a key treatment modality for many cancers. One percent of patients who receive ICIs can develop insulin deficient ICI associated diabetes (ICI-DM). These patients often have complex oncologic therapy plans making treatment of newly diagnosed insulin deficient diabetes challenging which often results in additional healthcare-related burden for the patient. Methods: This is a retrospective case series of five adults who developed ICI-DM after receiving either PD-1, CTLA-4 or PDL-1 inhibitors or a combination. Data on demographics, medical history and labs were collected in addition to mode of glucose monitoring and treatment after diagnosis of ICI-DM. Results: Patients were age 44-72 at diagnosis of ICI-DM, three were female. Two were admitted to the hospital in DKA, one was diagnosed in the ER with severe hyperglycemia without DKA, two had outpatient hyperglycemia without DKA. Glucose at diagnosis ranged from 215-510 mg/dL. C-peptide was low for all patients. Fingerstick blood sugar (FSBS) monitoring and basal/bolus insulin was immediately initiated for all patients. All were transitioned from FSBS to continuous glucose monitor (CGM) and 2/5 ultimately transitioned to sensor-augmented insulin pump therapy (AID). Time in range on CGM improved in four patients with percent time in range improving between 10-48%. In two patients, hypoglycemia frequency declined by 6% and 3%. Hyperglycemia frequency declined by 13% and 48% in patients on AID therapy and by 14% and 25% in two of those on basal/bolus insulin therapy. All patients preferred CGM over FSBS and remained on CGM therapy. Those who chose AID preferred it over basal/bolus insulin therapy stating it was less complicated than basal/bolus insulin with CGM. Conclusions: We report successful treatment of five cases of ICI-DM with CGM + basal/bolus insulin or AID. 80% demonstrated improved time in range and decreased overall frequency of hyperglycemia. 40% had decreased frequency of hypoglycemia. CGM allows for dynamic adjustment of insulin therapy in a population with complex medical regimens resulting in fluctuating glucose levels. The integrated pump and sensor technology in AID was less burdensome than basal/bolus in those who chose it. Managing ICI-DM is complicated. The burden of this entity can be lessened by harnessing the power of diabetes technology. Presentation: 6/2/2024

8637 Pituicytoma mimicking Craniopharyngioma

Abstract Disclosure: O. Araoye: None. T. Delibasi: None. A. Chaugule: None. S.K. Dhillon: None. C. Fuller: None. Pituicytoma, a rare low-grade glial tumor originating from the neurohypophysis or infundibulum of the pituitary gland, poses diagnostic challenges due to its propensity to mimic other sellar or suprasellar lesions. We present a case of a 51-year-old male with a history of a suprasellar mass initially suggested to be a craniopharyngioma, incidentally discovered. Opting for elective surgery, the patient underwent transsphenoidal resection, revealing a highly vascular tumor adherent to the optic chiasm and pituitary stalk. While the tumor was successfully removed, sacrifice of the pituitary stalk led to postoperative complications, including cerebrospinal fluid (CSF) leak and central diabetes insipidus (DI).Histopathological examination characterized the tumor as oncocytic pituicytoma/spindle cell oncocytoma, a subtype of pituicytoma. The anti-mitochondrial antibody staining at an external laboratory displayed diffuse granular cytoplasmic staining supporting oncocystic pituicytoma/spindle cell oncocytoma.Postoperatively, the patient developed central DI treated initially with desmopressin (DDAVP), complicated by subsequent hyponatremia necessitating salt tablets and fluid restriction. Additionally, central adrenal insufficiency was managed with hydrocortisone, and central hypothyroidism with levothyroxine. A history of testosterone deficiency was addressed through testosterone injections every 10 weeks.Pituicytoma's diagnostic complexity arises from nonspecific radiological features, requiring reliance on histology and immunohistochemistry for definitive diagnosis. The expression of TTF1 emerges as a characteristic marker. Surgical resection, the primary treatment modality, proves curative in most cases, albeit with associated morbidity including CSF leak, DI, and panhypopituitarism. The role of adjuvant radiotherapy remains uncertain, potentially considered in cases of incomplete resection or recurrence.This case emphasizes three key aspects: first, the potential misdiagnosis of a lobulated suprasellar mass as craniopharyngioma when it could be pituicytoma; second, the development of postoperative DI due to pituitary stalk involvement; and third, the importance of considering pituicytoma in the differential diagnosis of sellar and suprasellar masses.In conclusion, pituicytoma, though rare, demands a nuanced diagnostic approach and comprehensive postoperative management to address potential complications and optimize patient outcomes. Presentation: 6/2/2024

MGMT methylation and its prognostic significance in inoperable IDH-wildtype glioblastoma: the MGMT-GBM study

IntroductionThe methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) promoter is a valid biomarker for predicting response to therapy with alkylating agents and, independently, prognosis in IDH-wildtype(IDH-w) glioblastoma. We aim to study the impact of its methylation in overall survival of the unresectable IDH-w glioblastoma undergoing biopsy and systemic treatment.MethodsWe collected six-year retrospective (2017–2023) data at a quaternary neurosurgery center for patients undergoing biopsy as the only surgical procedure for an unresectable IDH wildtype glioblastoma. Data was collected from patient records including neuro-oncology multidisciplinary team meeting (MDT) documentation. Patients were grouped into categories according to different types of treatment received after biopsy (no treatment, chemotherapy (CT), radiotherapy (RT), chemoradiotherapy (CRT), chemoradiotherapy with adjuvant temozolomide (CRT with adjuvant TMZ), EORTC-NCIC protocol followed by second line treatment) and according to methylation status (unmethylated (< 5%), borderline methylated (5–15%) and strongly methylated (> 15%)). Survival analysis was performed.Results166 glioblastoma IDH wildtype patients were included in the study with mean age of 62.5 years (M: F = 1.5: 1). 70 (49.3%) patients had unmethylated MGMT status (< 5%), 29 (20.4%) patients had borderline methylated MGMT status (5–15%) and 43 (30.2%) patients had methylated MGMT status (> 15%). 36 (25.3%) patients did not receive any treatment post biopsy, 13 (9.1%) received CT only, 27 (19%) RT only, 12 (8.4%) CRT, 33 (23.2%) CRT with adjuvant TMZ, whereas 21 (14.7%) received EORTC-NCIC protocol along with second line treatment.In biopsy only group, there was no notable difference in survival outcomes among the different methylation statuses. For biopsy and any-other-form-of-treatment methylated groups showed a distinct trend of better survival compared to the borderline or unmethylated groups. Overall, methylated patients had better survival as compared to unmethylated or borderline groups.ConclusionMethylated MGMT status are predictors for better overall survival in unresectable IDH wildtype glioblastoma patients undergoing biopsy and treatment regardless of the treatment modality.

Targeted blood-brain barrier penetration and precise imaging of infiltrative glioblastoma margins using hybrid cell membrane-coated ICG liposomes

Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins.Graphical abstract

7956 Assessing Factors Influencing Polycystic Ovarian Syndrome Using Hybrid Multi-Criteria Decision Analysis

Abstract Disclosure: N.B. Trivedi: None. J. Amin: None. M. Patel: None. S. Patel: None. P. Rana: None. A. Rajani: None. V. Dave: None. Polycystic Ovarian Syndrome (PCOS) is a complex hormonal disorder having multifactorial origins. This study aims to apply Multi-Criteria Decision Analysis (MCDA) methods like Decision Making Trial and Evaluation Laboratory (DEMATEL) and Analytical Hierarchy Process (AHP) to prioritize factors influencing PCOS. In our study, 10 criteria impacting PCOS were identified through extensive literature review. AHP and DEMATEL were used via matrices, assessed by 13 experts. AHP determined relative importance/weights while DEMATEL assessed interconnectedness among criteria. AHP revealed that family history held the highest weight (0.22) while Insulin resistance held the lowest weight at 0.04. The results obtained from DEMATEL indicated that factors like obesity, insulin resistance, diet, psychological stress and sedentary lifestyle displayed higher D+R values, suggesting a strong influence on other factors; indicating their significant impact on the syndrome. The division of criteria into cause and effect groups based on D-R values revealed that family history, environmental factors, diet, sedentary lifestyle and psychological stress appear to be causative and sleep disturbances, low-grade inflammation, excess androgen and insulin resistance seem to be the consequences of PCOS. In AHP the criteria are treated as being independent to each other and their hierarchal order is determined. However, in realistic scenarios factors may have some sort of interdependency/relationship with one another. To identify that interdependency which AHP fails to focus on, DEMATEL was used. DEMATEL ensues that Insulin resistance along with obesity, sedentary lifestyle, and psychological stress show strong level of influence and interconnectedness, indicating a significant impact on the syndrome. However, insulin resistance, when treated as an independent criterion in AHP, displays lower weightage. In the end, improved PCOD treatment would come from targeted interventions and strategies that centre on the variables with a higher D+R value. When the criteria were considered independent of each other in AHP, highest weight is conferred to family history (despite of it having moderately low level of influence/interconnectedness on other criteria as ensued from DEMATEL) thus prompting more research in the direction of investigating genetic and familial factors associated with PCOS. This could consequently lead to early diagnosis and effective long term management. The combined methodology (DEMATEL+AHP) ensures comprehensive assessment of PCOS factors. Previous studies might have focused on individual factors separately or failed to adequately explore their interrelationships and relative importance. MCDA can be further employed in healthcare to assess conflicting treatment modalities, risk factors etc. for other multifactorial disorders. Presentation: 6/2/2024

Spatiotemporal spread of oncolytic virus in a heterogeneous cell population

Oncolytic (cancer-killing) virus treatment is a promising new therapy for cancer, with many viruses currently being tested for their ability to eradicate tumors. One of the major stumbling blocks to the development of this treatment modality has been preventing spread of the virus to non-cancerous cells. Our recent ability to manipulate RNA and DNA now allows for the possibility of creating designer viruses specifically targeted to cancer cells, thereby significantly reducing unwanted side effects in patients. In this study, we use a partial differential equation model to determine the characteristics of a virus needed to contain spread of an oncolytic virus within a spherical tumor and prevent it from spreading to non-cancerous cells outside the tumor. We find that oncolytic viruses that have different infection rates or different cell death rates in cancer and non-cancerous cells can be made to stay within the tumor. We find that there is a minimum difference in infection rates or cell death rates that will contain the virus and that this threshold value depends on the growth rate of the cancer. Identification of these types of thresholds can help researchers develop safer strains of oncolytic viruses allowing further development of this promising treatment.

Vitreoretinal Surgery in Pediatric Patients with Vitreoretinal Pathology Secondary to Uveitis

In pediatric uveitis, as with all forms of uveitis, the primary treatment modality involves achieving systemic and local immunosuppression through pharmacotherapy. However, due to the challenge of articulating symptoms by patients in the younger age group, resulting in delayed presentation to clinicians, or the tendency for uveitis to manifest more quietly in this age group, pediatric uveitis cases can be diagnosed late, unfortunately presenting with secondary complications at the time of diagnosis. In these patients, after appropriate immunosuppression is achieved, vitreoretinal surgery may be necessary to address vitreoretinal complications. Additionally, in cases where etiology cannot be determined by non-invasive methods, or when there is inadequate response or no response to treatment, rapid progression of inflammation threatening the optic nerve and macula, or suspicion of malignancy, diagnostic vitreous sampling or chorioretinal biopsy via vitreoretinal surgery may be pursued. The aim of this review is to evaluate the role and significance of vitreoretinal surgery in pediatric uveitic eyes.

Treatment Strategies for Sigmoid Volvulus : A case series of 15 patients

Sigmoid volvulus, a condition characterized by the twisting of the sigmoid colon, is a frequent cause of large bowel obstruction. This study aims to review and evaluate the treatment strategies applied to 15 patients diagnosed with sigmoid volvulus at our institution. The outcomes, complications, and long-term results were analyzed to identify the most effective management approaches. The treatment modalities ranged from conservative management to surgical interventions. Our findings indicate that a multidisciplinary approach, timely intervention, and appropriate patient selection are key determinants of successful outcomes.

A novel 3D printed model for educating medical students on limb fractures: a randomized controlled preliminary study

BackgroundMedical education related to bone fracture must address numerous challenges including complex anatomical characteristics, diverse injury mechanisms, fracture typing, and treatment modalities. Our newly developed 3D printed model comprises components that may be combined or split to simulate various anatomical features, fracture types, and treatment modalities. This study aims to analyze the teaching utility of the new 3D-printed model compared with the traditional solid model.MethodsThis prospective study included 112 students randomly assigned to fracture-related education with a conventional model or the newly developed 3D-printed model. All students received 40 min of lecture, 20 min for femoral neck and 20 min for tibiofibular fractures, and a post-class quiz (10 min each) immediately followed. Scores on tests of fracture-related knowledge and user satisfaction were measured pre and post education for comparison.ResultsThe 3D printing group had an advantage in retention of anatomic knowledge, fracture typing and choice of treatment for the femoral neck fracture (P < 0.05). For the tibiofibular fracture the 3D printing group had an advantage in retention of anatomic knowledge and fracture complications (P < 0.05).Scores on the questionnaire survey also showed increased satisfaction in the 3D-printed model group(P < 0.05).ConclusionsThe proposed 3D-printed model can enhance the teaching effect significantly and has potential for widespread use in medical student education.

APMCG-1 attenuates ischemic stroke injury by reducing oxidative stress and apoptosis and promoting angiogenesis via activating PI3K/AKT pathway

Ischemic stroke (IS) is a major cause of mortality and morbidity worldwide. Beyond thrombolysis, strategies targeting anti-oxidative apoptosis and angiogenesis are considered prospective therapeutic strategies. Nevertheless, existing natural and clinical remedies have limited efficacy in the management of IS. Moreover, despite their millennial legacy of IS remediation, natural remedies such as ginseng incur high production costs. The novel glycopeptide APMCG-1, extracted from mountain-cultivated ginseng dregs in our previous study, is a potent therapeutic candidate for IS. This study investigated APMCG-1's remedial mechanisms against IS injury using an H2O2-induced oxidative stress paradigm in human umbilical vein endothelial cells (HUVECs) emulating ischemic endothelial cells, in a ponatinib-induced zebrafish IS model, and in rat middle cerebral artery occlusion (MCAO) prototypes. Cellular assays confirmed the proficiency of APMCG-1 in preventing oxidative stress and cell death, fostering regeneration, and facilitating neovascularization within the H2O2-stressed HUVECs framework. Moreover, APMCG-1 augmented hemodynamic velocity, oxidative stress mitigation, apoptosis reduction, and motor enhancement in a zebrafish model of IS. In MCAO rats, APMCG-1 ameliorated neurological deficits and cerebral injury, as evidenced by increased neurological scores and diminished infarct dimensions. In cells and animal models, APMCG-1 activated the PI3K/AKT signaling pathway, modulating factors such as Nrf2, Bcl-2, Caspase 3, eNOS, and VEGFA, thereby ameliorating cellular oxidative distress and catalyzing angiogenesis. Collectively, these results demonstrate the potential protective effects of APMCG-1 in IS pharmacotherapy and its prospective utility as an herbal-derived IS treatment modality.

Symmetrical peripheral gangrene caused by urosepsis: Case reports and literature review.

Symmetrical peripheral gangrene (SPG) is a serious and rare complication in patients with urosepsis, characterized by distal limb symmetry impairment. In this study, 3 cases of SPG caused by urosepsis were reported, and the Chinese and English literature on SPG caused by urosepsis was reviewed. The demographic, clinicopathological, treatment, and follow-up data of the patients were summarized and analyzed. SPG was diagnosed with clinical symptoms. We conducted urological invasive surgery, administered anti-infective therapy, implemented fluid resuscitation and blood product transfusion, provided mechanical ventilation support, optimized myocardial contractility, administered heparin and B vitamins, utilized papaverine for vasodilation, performed hemodialysis and plasma exchange, peripheral skin warming along with other treatment modalities. Two patients died and 1 patient underwent autoamputation. Our cases and literature review demonstrate that timely and accurate diagnosis, effective infection control, correction of hypoperfusion, organ function support, early management of disseminated intravascular coagulation, avoidance of premature amputation, and multidisciplinary comprehensive treatment are crucial for the successful treatment of SPG caused by urosepsis.

Large-scale screening identifies enzyme combinations that remove in situ grown oral biofilm

Bacteria in the oral cavity are responsible for the development of dental diseases such as caries and periodontitis, but it is becoming increasingly clear that the oral microbiome also benefits human health. Many oral care products on the market are antimicrobial, killing a large part of the oral microbiome but without removing the disease-causing biofilm. Instead, non-biocidal matrix-degrading enzymes may be used to selectively remove biofilm without harming the overall microbiome.The challenge of using enzymes to degrade biofilms is to match the narrow specificity of enzymes with the large structural diversity of extracellular polymeric substances that hold the biofilm together. In this study, we therefore perform a large-scale screening of single and multi-enzyme formulations to identify combinations of enzymes that most effectively remove dental biofilm.We tested >400 different treatment modalities using 44 different enzymes in combinations with up to six enzymes in each formulation, on in vitro biofilms inoculated with human saliva. Mutanase was the only enzyme capable of removing biofilm on its own. Multi-enzyme formulations removed up to 69 % of the biofilm volume, and the most effective formulations all contained mutanase. We shortlisted 10 enzyme formulations to investigate their efficacy against biofilms formed on glass slabs on dental splints worn by 9 different test subjects. Three of the ten formulations removed more than 50 % of the biofilm volume. If optimal enzyme concentration and exposure time can be reached in vivo, these enzyme combinations have potential to be used in novel non-biocidal oral care products for dental biofilm control.

Allergen Immunotherapy for the Prevention and Treatment of Asthma.

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease-modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease-modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma. Trial Registration: clinicaltrials.gov identifier: NCT06027073.

MicroRNA Expression in Exosome Extracellular Vesicles as Targets for Personalized Medicine in Diffuse Large B Cell Lymphoma Patients with HIV Infection.

Extracellular Vesicles (EVs), more specifically exosomes (xEVs), have been associated with Diffuse Large B-cell Lymphoma (DLBCL). These xEVs contain a variety of biomolecules, such as proteins and nucleic acids (e.g., microRNA, LncRNA, and DNA). The expressions of these vesicles in the setting of Human Immunodeficiency Virus (HIV) have been linked to disease progression. Studies have explored the use of EVs in more practical clinical settings. Several studies have found that biomolecules within xEVs can serve to detect disease progression. The biomolecule content within xEVs is useful in prognostication and has even been associated with mechanisms of resistance for some DLBCL treatment modalities. This review article explores the role of xEV biomolecule content in DLBCL progression in the context of HIV infection and its applied use in practical disease management.

A systematic review of case reports on mortality, modes of infection, diagnostic tests, and treatments for Nipah virus infection.

First identified in Malaysia in 1998, the Nipah virus is a paramyxovirus related to the Hendra virus. The clinical manifestation can vary from a silent infection to a life-threatening encephalitis. The World Health Organization (WHO) has documented 25 outbreaks in South Asia, resulting in 429 cases and 307 deaths to date. Currently, there are no approved treatments for the deadly Nipah virus infection, which is a serious threat to public health worldwide. Consequently, a review was conducted to examine the geographic distribution of the Nipah virus, mortality, transmission pathways, and available methods for diagnosis and treatment. PubMed, Scopus, Web of Science, and Google Scholar servers were used to conduct a systematic search in compliance with the PRISMA guidelines. The results were tabulated and analyzed. A total of 12 studies (7 case series and 5 case reports) were included in the final analysis, and 92 cases were analyzed. The most frequent symptoms were fever (80%), myalgia (47%), headache (47%), shortness of breath/acute respiratory distress syndrome (n = 44.1%), altered sensorium (44.1%), and vomiting (42.6%). The most commonly used diagnostic test was RT-PCR (45.5%). The most common route of transmission reported is direct human contact with the infected patients. Treatment modalities include interventional procedures, antiviral drugs, and symptomatic treatment. The most common complications were seizures (39.2%) and altered sensorium (35.7%). The mortality rate was 73.9%. It is crucial to emphasize the importance of early Nipah virus infection diagnosis and treatment to prevent life-threatening consequences.

Current status and future perspectives for endoscopic treatment of local complications in chronic pancreatitis.

Chronic pancreatitis is a progressive disease characterized by irregular fibrosis, cellular infiltration, and parenchymal loss within the pancreas. Chronic pancreatitis treatment includes lifestyle modifications based on disease etiology, dietary adjustments appropriate for each stage and condition, drug therapy, endoscopic treatments, and surgical treatments. Although surgical treatments of symptomatic chronic pancreatitis provide good pain relief, endoscopic therapies are recommended as the first-line treatment because they are minimally invasive. In recent years, endoscopic therapy has emerged as an alternative treatment method to surgery for managing local complications in patients with chronic pancreatitis. For pancreatic stone removal, a combination of extracorporeal shock wave lithotripsy and endoscopic extraction is used. For refractory pancreatic duct stones, intracorporeal fragmentation techniques, such as pancreatoscopy-guided electrohydraulic lithotripsy and laser lithotripsy, offer additional options. Interventional endoscopic ultrasound has become the primary treatment modality for pancreatic pseudocysts, except in the absence of disconnected pancreatic duct syndrome. This review focuses on the current status of endoscopic therapies for common local complications of chronic pancreatitis, including updated information in the past few years.