Distinct Clinical Entity Research Articles

Early-onset lupus nephritis.

Early-onset systemic lupus erythematous (SLE) is a distinct clinical entity characterized by the onset of disease manifestations during childhood. Despite some similarities to patients who are diagnosed during adulthood, early-onset SLE typically displays a greater disease severity, with aggressive multiorgan involvement, lower responsiveness to classical therapies, and more frequent flares. Lupus nephritis is one of the most severe complications of SLE and represents a major risk factor for long-term morbidity and mortality, especially in children. This review focuses on the clinical and histological aspects of early-onset lupus nephritis, aiming at highlighting relevant differences with adult patients, emphasizing long-term outcomes and discussing the management of long-term complications. We also discuss monogenic lupus, a spectrum of conditions caused by single gene variants affecting the complement cascade, extracellular and intracellular nucleic acid sensing and processing, and occasionally other metabolic pathways. These monogenic forms typically develop early in life and often have clinical manifestations that resemble sporadic SLE, whereas their response to standard treatments is poor.

Brilacidin, a host defense peptide mimetic, potentiates ibrexafungerp antifungal activity against the human pathogenic fungus Aspergillus fumigatus.

Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Aspergillus fumigatus causes a series of distinct invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. A. fumigatus causes a spectrum of distinct clinical entities named aspergillosis, which the most severe form is the invasive pulmonary aspergillosis. There are few therapeutic options for treating aspergillosis and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a synergizer o fibrexafungerp (IBX) against A. fumigatus. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. We propose the combination of BRI and IBX as a new antifungal combinatorial treatment against aspergillosis.

Targeting the Manifestations of Subclinical and Overt Hypothyroidism Within the Hippocampus.

The past decade has witnessed a surge of articles describing the neurocognitive sequelae and associated structural and functional brain abnormalities of patients with overt hypothyroidism (OH) and subclinical hypothyroidism (SCH). Findings show effects primarily within the frontal lobes with usually worse outcomes for OH than SCH. Several recent studies have also indicated hypothyroid patients may have smaller hippocampi, a key structure for memory. The JCEM paper by Zhang and colleagues applies 2 novel approaches for analyzing hippocampal structure and function. One uses an automated processing tool that segments the hippocampus into distinct subregions, and the other performs connectivity analysis to assess the relationships between specific hippocampal subregions and cortical areas. Relatively large samples of OH and SCH patients and healthy controls received a test of global cognitive functioning and underwent structural and functional magnetic resonance imaging. Results showed hypothyroid groups scored significantly below controls on the memory scale and also had smaller hippocampal volumes in selective subregions. Effects were stronger for SCH than OH groups, who also showed different patterns of interconnectivity between hippocampal subregions and specific frontal lobe areas. To make sense of these findings, I explored the rodent and human literatures on thyroid hormone's role in hippocampal functioning and on hippocampal subfields and their purported functions and interconnections. Because current results suggest SCH may represent a distinct clinical entity with unique brain manifestations, I hypothesized 2 explanations for these findings, one involving transporter defects in the brain barriers and the other, differential neurodegeneration of the blood-brain barrier vascular unit.

PATH-14. A CLINICAL CONUNDRUM - INFANTILE POSTERIOR FOSSA EPENDYMOMA WITH YAP1:MAML FUSION?

Abstract BACKGROUND Ependymomas of infancy (0-18months) have been reported to comprise distinct clinical, pathological and genetic entities. Young age is typically associated with posterior fossa group A (PF-A) tumours and therefore a poor prognosis. Treatment of these infants is challenging with limited therapeutic options that have significant long-term sequelae. METHOD We report a single case of a 4-month old baby girl who presented with obstructive hydrocephalus and a presumed posterior fossa mass. RESULTS Imaging demonstrated a large fairly well-defined solid lesion with multiple T1 high and corresponding T2 intermediate signal intensity foci scattered throughout the lesion and marked mass effect on the cerebellum and fourth ventricle. The lesion was inseparable from the pineal gland, habenula and tectum and only mild diffusion restriction. Whilst initially considered to be a posterior fossa tumour, the presence of a claw sign with the tectal plate, favoured a tectal origin. Histological appearances, together with immunohistochemistry findings (GFAP positive and EMA patchy perinuclear dot expression) were consistent with classic ependymoma. Grading was difficult as mitotic activity was relatively low, although focal areas of high ki67 proliferation index were noted suggesting at least focal grade 3 areas. Retained expression of tumour cells for H3K27me3 on immunohistochemistry suggested the likely posterior fossa group B (PF-B) ependymoma. Local SNP chromosome microarray found no acquired clonal abnormality; with no detection of gain chromosome 1q; loss/LOH 6q; Loss/LOH 9p21.3 [CDKN2A, CDKN2B], chromothripsis 11q [ZFTA::RELA], Loss/LOH 17p13 [TP53] or Loss/LOH 22q [NF2]. Additional NGS sequencing identified a YAP1::MAML2 fusion (confirmed with targeted RT-PCR followed by subsequent Sanger sequencing). CONCLUSION This case highlights the challenges with overlapping clinical, pathological and radiological features in an infant with ependymoma, necessitating a molecular diagnosis. After 21months, the patient remains in complete remission following surgery alone.

A Case Series on Spotted Fever and Typhus Fever Seropositivity at National Center for Disease Control and Epidemiological Perspective.

Background: The rickettsioses, except for typhus fever and scrub typhus (ST), were not really recognized as distinct clinical entities until the early 20th century. Only when specific rickettsial serologic testing was introduced in the 1940s could the precise etiologies of various rickettsial diseases (RDs) be determined with certainty. Although ST is a well- recognized zoonotic disease entity, but non-scrub typhus rickettsial infection like spotted fever group and typhus group are not well studied in India and are still underestimated. Methods: We report cases who had shown seropositivity of spotted fever and typhus fever RD in IgM and IgG ELISA whose samples were referred from various hospitals of Delhi/National Capital Region in which clinicians had strong suspicion of rickettsiosis other than ST or Weil-Felix test found positive for any of the OX2, 19, and K antigens. Results: We reported 18 cases of SFG and TGRD with mostly cases presented with fever followed by hepato-intestinal symptoms. Conclusion: The vast variability and nonspecific presentation of rickettsiosis in spotted and typhus fever at times have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications, and in turn, reduces morbidity and mortality owing to RDs. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy for these infections.

Prevalence and Management of Premenstrual Dysphoric Disorder (PMDD): Literature Review

Premenstrual Dysphoric Disorder (PMDD) is a severe form of premenstrual syndrome (PMS) characterized by significant mood disturbances and functional impairment. It affects approximately 3-8% of menstruating women and has been recognized as a distinct clinical entity by the American Psychiatric Association in the DSM-5. Recent studies have emphasized the global prevalence of PMDD and its substantial impact on daily functioning, relationships, and overall mental health. Understanding its prevalence of PMDD helps in recognizing the scale of the problem and the need for targeted interventions. This literature review provides an overview of the current understanding of PMDD, including its pathophysiology, diagnosis, and treatment options. As a result, it was observed that there exist a high prevalence of Premenstrual syndrome and Premenstrual Dysphoric Disorder among Indian females of reproductive age group that consequently affects the quality of life adversely.

Immune checkpoint inhibitor associated epidermal necrosis, beyond SJS and TEN: a review of 98 cases.

Immune checkpoint inhibitor (ICI) therapies carry the risk of major immune-related adverse events (irAEs). Among the most severe irAEs is epidermal necrosis that may clinically mimic Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The aim of this study was to provide a summary of the clinical and histological features of ICI-associated epidermal necrosis, with a special focus on factors associated with fatal outcomes in cases of extensive disease. A total of 98 cases, 2 new cases and 96 reported on PubMed and in the literature, of ICI-associated epidermal necrosis were assessed. Development of epidermal necrosis occurred between 1day and 3 years after starting ICI therapy, with an average onset of 13.8 weeks for patients with limited (< 30% BSA) and 11.3 weeks for those with extensive (≥ 30% BSA) involvement, and a median onset of 5.8 weeks and 4 weeks respectively. A preceding rash was seen in 52 cases and was more common in extensive cases. Mucosal involvement was only reported in 65% of extensive cases but was significantly associated with fatal reactions. Co-administration of cytotoxic chemotherapy was associated with more extensive disease. Recovery was observed in 96% and 65% of those with limited and extensive involvement respectively and no specific therapy was associated with improved survival. Young age was significantly associated with poor outcomes in extensive disease, the average age of surviving patients was 64.5 years old versus 55.1 years old for deceased patients, p < 0.01. Both superficial perivascular and interface/lichenoid inflammatory infiltrates were commonly seen. These findings suggest that ICI-associated epidermal necrosis should be considered a distinct clinical entity from drug-induced SJS/TEN.

An Unusual Localization of Spinoglenoid Cysts in the Shoulder; Case Report and Comprehensive Literature Analysis

Objective: A spinoglenoid cyst represents a distinctive clinical entity within the realm of shoulder pathology, characterized by the development of a cystic structure in the spinoglenoid notch. Situated in the intricate anatomy of the shoulder, this cyst often involves compression of the suprascapular nerve, introducing a spectrum of symptoms that range from localized discomfort to functional impairment. As an area of increasing interest in orthopedic and neurological literature, the spinoglenoid cyst poses diagnostic and therapeutic challenges. Case: Patient 1: A 31-year-old male presented with right shoulder pain and a positive Hawkins sign. He had a history of bicipital tendinitis. T2-weighted MRI (T2WI) showed a hyperintense 14x16mm spinoglenoid cyst. Patient 2: Another 31-year-old male presented with shoulder pain, positive Hawkins and Neer signs, and pain induced upon shoulder range of motion. T2-weighted MRI (T2WI) revealed a 16x11mm hyperintense ganglion cyst with hypointense septae. Patient 3: A 42-year-old male presented with shoulder pain that started a month ago. He had a history of rotator cuff syndrome, shoulder impingement syndrome, and adhesive capsulitis in the shoulder, along with positive Hawkins and Neer signs. T2-weighted MRI (T2WI) identified a 25x15x28mm hyperintense ganglion cyst. Conclusion: The cases presented highlight the diagnostic challenges posed by spinoglenoid cysts and the importance of advanced imaging techniques, particularly MRI, in confirming their presence and understanding their characteristics. The diverse clinical manifestations, ranging from chronic shoulder pain to neurological deficits, emphasize the need for a nuanced and individualized approach to diagnosis and management.

#2139 Non-lupus full house nephropathy: a debatable entity

Abstract Background and Aims The presence of a full house (FH) pattern at immunofluorescence on kidney biopsy in a patient without clinical and laboratory features of systemic lupus erythematosus (SLE) has led to the descriptive term non-lupus full house nephropathy (NLFHN). This systematic review and meta-analysis focus on NLFHN nomenclature, clinical findings and outcomes. Method In a reiterative process, all identified terms for NLFHN and other MeSH terms were searched in PubMed. Out of 344 results, 57 records published between 1982 and 2022 were included in the analysis. Clinical data of single patients from different reports were collected and analysed. Results Out of the 57 records, 61% were case reports. NLFHN was addressed with 17 different names; the same name used by different authors could refer to different entities. We identified 148 patients: 75 (51%) were males; median age 35 (23-58) years. Serum creatinine and proteinuria at onset were 1.4 (0.8-2.5)mg/dL and 5.7 (2.7-8.8)g/day. Overall, about half of patients achieved complete response. A causative agent was identified in 51 (44%) patients, predominantly infections(41%). Secondary NLFHN was mostly non-relapsing with worse kidney function at onset compared to idiopathic NLFHN (P = 0.001). Among the 57 (50%) patients with idiopathic NLFHN, complete response was comparable between patients treated with immunosuppression and supportive therapy; however, proteinuria and creatinine at onset were higher in patients treated with immunosuppression (P = 0.089 and P = 0.066). The remaining 7 (6%) patients developed SLE after a median follow-up of 5.0 (1.9-9.0) years. Conclusion The place of NLFHN among glomerular diseases is still uncertain, due to the lack of high-quality evidence and consensus on nomenclature. NLFHN can be evaluated as initial manifestation of SLE, isolated manifestation of SLE or a new disease unrelated to SLE. Data support the classification of SLE and NLFHN as distinct clinical entities, with comparable outcome. However, RCTs are needed to drive strong conclusions on treatments and outcomes.

Prevalence, incidence, mortality and healthcare resource use for generalized pustular psoriasis, palmoplantar pustulosis and plaque psoriasis in England: a population-based cohort study.

Generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) are chronic inflammatory skin conditions. Accumulating evidence shows that GPP and PPP have different characteristics to plaque psoriasis and are distinct clinical entities. To assess the epidemiology, comorbidities, mortality and healthcare use for patients in England with GPP and PPP versus those with plaque psoriasis. We carried out a cohort study involving analyses of longitudinal electronic health record data in the Clinical Practice Research Datalink Aurum database and linked hospital and mortality data between 2008 and 2019. The primary study outcome was the incidence and prevalence rates of GPP, PPP and plaque psoriasis in England. Secondary outcomes included survival rates and healthcare resource use (HCRU) by disease type. We identified 373 patients with GPP, 1828 with PPP and 224 223 with plaque psoriasis. Mean (SD) age was 55.9 (18.6) years for patients with GPP, 51.5 (16.4) years for those with PPP and 48.5 (19.1) years for those with plaque psoriasis; 62.5% and 65.9% of patients with GPP and PPP, respectively, were women, vs. 49.4% of those with plaque psoriasis. About half of patients were overweight or obese at baseline (GPP 48.6%, PPP 56.0%, plaque psoriasis 45.9%). The incidence rates for GPP, PPP and plaque psoriasis were 0.25 [95% confidence interval (CI) 0.21-0.28], 2.01 (95% CI 1.92-2.11) and 103.2 (95% CI 102.5-103.9) per 100 000 person-years, respectively. From 2008 to 2019, the prevalence rates per 100 000 persons ranged from 1.61 to 3.0 for GPP, from 1.1 to 18.7 for PPP and from 1771.0 to 1903.8 for plaque psoriasis. Survival rates were lower for patients with GPP, particularly those who were > 55 years of age and those with a history of one or more comorbidities in each cohort. HCRU was lower in the cohort with plaque psoriasis and highest in the cohort with GPP, particularly among those who had more than one GPP flare. Our results provide further evidence that, in England, GPP is a distinct disease with different epidemiology, lower survival and higher HCRU than plaque psoriasis.

Hidradenitis suppurativa: definition, epidemiology, etiology, diagnosis (part 1)

Hidradenitis suppurativa (HS) is a chronic recurrent skin disease characterized by development of autoimmune inflammation in the infundibulum of the hair follicle and apocrine sweat glands located in the axillary, inguinal, anogenital regions, submammary folds, near the areola of mammary glands and the umbilical region. HS is difficult to treat and has an extremely negative impact on the quality of life. HS is separated into a distinct clinical entity fundamentally different in etiopathogenesis from acute bacterial hidradenitis. The exact prevalence of HS is unknown, it varies greatly in different studies ranging from 0.03 to 4% in general population. The detection of IL-1β, IL-23, and IL-17 in the lesions indicates the key role of autoimmune inflammation involving Th17-lymphocytes in the pathogenesis of HS. Risk factors include smoking, obesity, mechanical friction, genetic predisposition. The diagnosis of HS relies on three obligatory criteria: characteristic distribution, typical morphology of the lesions and relapsing, chronic disease course. There is no “gold standard” in assessing the severity of the disease, since all available scoring systems have many limitations, therefore many questions regarding this disease remain unsolved at present — from terminology and clear and most objective assessment criteria for the severity of the process to the development of native clinical guidelines.

Early-Onset Colorectal Cancer-A Retrospective Study from a Tertiary Referral Hospital in Romania.

Early-onset colorectal cancer emerges as a distinctive clinical and biological entity and is generally defined as the onset of colon or rectal neoplasia before the age of 50. Several reports describe an increasing incidence worldwide of colorectal cancers occurring in individuals younger than 50 years, along with particular histologic and molecular features. Although heredity may be an explanation in some cases with young-onset colorectal cancer, other driving factors remain partially unknown. The present study explores demographic, clinical, and pathological features within a group of patients diagnosed with colorectal cancer before the age of 50. It is a retrospective survey based on data collected between 2017 and 2023 within three surgical departments from a tertiary Romanian hospital. The clinical and pathological features we identified (later-stage disease, distal colon tumor localization, mucinous histology) are mainly superimposed with the existing data in the literature regarding this pathology. In order to lower the burden that colorectal neoplasia diagnosed in the young implies, a change of paradigm should be made in terms of establishing effective and targeted screening programs but also in the direction of enhancing complex clinical, pathological, and molecular diagnosis.

Circumscribed Thinning of the Calvaria - A Long-Term Sequela After Vacuum Extraction Delivery

Abstract Background Vacuum extraction deliveries are associated with a number of complications like injuries to the skin, subperiosteal, subgaleal and intracranial hemorrhages. Even skull fractures have been described, but data on persistent changes in the bone structure of the skull like thinning of the calvaria is lacking in the literature. Aims We describe a previously unreported long-term sequela of vacuum extraction delivery. Methods We present a series of 8 children, who were referred because of an irregularity of the cranial surface without other symptoms. The investigations revealed a circumscribed thinning of the calvaria in all 8 cases. Detailed history and the specific clinical findings were crucial in the assessment. Various imaging techniques were used to visualize the lesions and rule out some differential diagnoses. Results All children had undergone a vacuum-assisted delivery. All irregularities of the cranial surface were discovered incidentally. Clinical examination revealed a round (6) or linear (1) channel-shaped indentation of the calvaria in 7 cases. The shape and size of the annular thinning of the calvaria matched devices commonly used in vacuum extraction very well. In one patient, a localized protrusion of the calvaria was investigated, but an indentation more posteriorly was detected in the CT scan. CT scan was performed in 6 patients, in 2, parents refused this examination. In the follow-up, no progression or symptoms was observed in any of the patients. Conclusion Such long-term sequelae after vacuum-assisted delivery have not been reported yet and the underlying mechanism is unclear. In children who present with irregularities of the cranium, an accurate history, including the mode of birth, and detailed clinical examination should be performed. Knowledge about the presented pathology may help to avoid extensive investigations, particularly CT scan. The publication of further cases could help to propagate the circumscribed thinning of the calvaria after vacuum extraction as a distinctive clinical entity.

Parenchymal Neuro-Behçet's disease or Comorbid Behçet's disease with multiple sclerosis: A discriminative analysis of a complex clinical entity

BackgroundPatients with Behçet's disease (BD) may rarely manifest with cerebral white matter lesions resembling multiple sclerosis (MS). This may result in misdiagnosis due to diagnostic difficulties between parenchymal neuro-BD (pNBD) and MS. This study aims to elucidate the distinguishing features of patients with comorbid BD and MS (BD+MS) in comparison to those with pNBD and MS alone by focusing on clinical and laboratory features. We also aimed to identify the distinctive characteristics of BD+MS patients by comparing them to patients with pNBD and MS. MethodsThe methodology of this study involved a retrospective analysis of patient records followed in the Department of Neurology at the Istanbul Faculty of Medicine, Istanbul University. The study population included patients diagnosed with pNBD, MS, and a comorbid condition of BD and MS (BD+MS). We assessed clinical, radiological, and laboratory data, including disease onset, annual relapse rates, Expanded Disability Status Scale (EDSS) progression, and cerebrospinal fluid examination. Several parameters were examined between the pNBD, MS, and BD+MS patient groups to find similarities and differences between subgroups. ResultsOur study included 1,764 patients: 172 with pNBD, 1,574 with MS, and 18 with BD+MS. A predominance of females was noted in the BD+MS (72%, p < 0.001) and MS (69 %, p < 0.001) groups compared to pNBD (30 %). The median age at the onset of neurological symptoms was 35.5 (IQR: 16.8) years for BD+MS, 34.6 (13.6) years for pNBD, and 27.6 (13.3) years for MS (BD+MS vs. MS; p = 0.3, pNBD vs. MS, p = 0.7). Additionally, the number of attacks was notably different, with BD+MS patients experiencing a median of 3.5 (2.0) attacks compared to 3.0 (3.0) for MS patients and only 1.0 (1.0) for pNBD patients, suggesting a more active disease course in the MS and BD+MS groups compared to pNBD (p < 0.001). The median annualized relapse rate for BD+MS was 0.3 (0.2), which was lower than the rate of 0.4 (0.4) in MS (p = 0.048) and equivalent to the rate of 0.2 (0.3) in pNBD (p = 0.2). The time to the first relapse was similar to those with BD+MS and MS, but considerably shorter than in individuals with pNBD (p < 0.0001). The cerebrospinal fluid (CSF) analysis showed no significant differences in neutrophil and lymphocyte counts between BD+MS and MS patients but elevated levels in pNBD patients (p < 0.05). CSF protein levels were consistent across all groups (p = 0.1 and p = 0.7). Oligoclonal bands were detected in all patients with BD+MS, in the majority of MS patients (83.6 %), and a small percentage of pNBD patients (19.7 %), showing a notable distinction between the BD+MS and pNBD groups (p < 0.001). ConclusionOur study underscores the need for a skeptical approach in diagnosing and treating patients with BD who exhibit symptomatic MS-like MRI lesions. Our findings suggest that BD+MS is a distinct clinical entity, warranting specific diagnostic and treatment approaches. Our findings highlight that BD patients with MS-like lesions meeting MS diagnostic criteria should be managed as patients with comorbid MS and BD rather than pNBD.

Is young adult idiopathic scoliosis a distinct clinical entity from adolescent idiopathic scoliosis? a Systematic Review and Meta-analysis comparing pre-operative characteristics and operative outcomes.

This study aims to conduct a systematic review of the literature comparing pre-operative, intraoperative, and post-operative characteristics between adolescent idiopathic scoliosis (AIS) and young adult idiopathic scoliosis (YAdIS) patients. Following PRISMA guidelines, we conducted a search of the PubMed/Medline, EMBASE, and Cochrane Central databases to identify full-text articles in the English-language literature. Our inclusion criteria were studies that compared preoperative, intraoperative, and postoperative characteristics between AIS and YAdIS patients. We performed a meta-analysis reporting mean difference (MD) for continuous variables and Odds ratios (ORs) to assess differences in postoperative complications. Seven studies consisting of 1562 patients were included in the meta-analysis. The AIS group exhibited less intraoperative bleeding and shorter surgical procedures, with a mean difference between groups of 122.3ml (95% CI 46.2-198.4, p = 0.002) and 28.7min (95% CI 6.5-50.8, p = 0.01), respectively. Although the preoperative Cobb angle did not differ between groups (p = 0.65), patients with AIS achieved superior postoperative deformity correction, with a mean difference of 7.3% between groups, MD -7.3 (95% CI -9.7, -4.8, p < 0.00001), and lower postoperative Cobb angles of the major curve, MD 4.2 (95% CI 3.1, 5.3, p < 0.00001). YAdIS patients were fused, on average, 0.2 more vertebral levels than AIS patients, MD 0.2 (95% CI 0.01, 0.5, p = 0.04). AIS patients experienced a significantly shorter length of stay after the surgical procedure, with an MD of 0.8days (95% CI 0.1, 1.6, p = 0.02). No significant difference was found between groups in terms of complications (p = 0.19). YAdIS should be regarded as a distinct surgical entity, characterized by increased bleeding, longer surgical duration, greater deformity correction challenges, and the need for fusion of additional vertebral levels compared to AIS. Surgeons should be mindful of these differences and discuss them with patients and their families, especially in cases where the correction of the AIS deformity is delayed and there is a high risk of progression after skeletal maturity. Further research is needed to explore alternative surgical techniques and enhance outcomes for YAdIS patients.

One-Point Technique in Brainstem Cavernous Malformation Surgery: Evaluation of Approaches and Outcomes From a Different Perspective.

Brainstem cavernous malformations (BCMs) are a distinct clinical entity that carry a high risk of patient morbidity because of location and risk of hemorrhage. Surgical management of these lesions requires intimate knowledge of surgical anatomy and skull base approaches. This article is intended to highlight a modern approach for the treatment of BCMs, with an emphasis on the use of the one-point technique to guide resection. We describe a case series of BCMs treated through a variety of skull base approaches, describing our decision-making strategy. We review the concept of the one-point technique focusing on the safest access to the malformation through 2 representative cases and also perform a retrospective review of 32 consecutive patients who underwent BCM resection to present outcomes and the comparison of two-point vs one-point techniques. Consecutive series of 32 patients in whom the one-point technique was used is presented. In 8 patients (25%), the traditional two-point technique would suggest a different trajectory than the one-point technique. Postoperative MRI confirmed complete resection in 30 patients (95%), and 29 patients (91%) had modified Rankin Scale (0-2) at follow-up. All patients in whom the one-point technique guided a different trajectory had gross total removal of the cavernous malformation, with one patient having long-term new neurological impairment from the surgery. There were no mortalities. Despite surgical advances in recent decades and more widespread understanding of surgical anatomy and safe entry zones, surgical resection of BCMs remains a formidable challenge. While not necessarily the shortest access, the one-point technique offers a safe approach considering all the different modalities in our armamentarium and can be used as part of a strategy to determine the optimal approach to resect BCMs.

Consequences of Clot Formation and Hyphema Post-Internal Trabeculotomy for Glaucoma.

Clot formation and hyphema following internal trabeculotomy represent distinct clinical entities. The eyes with clot formation exhibited a more pronounced postsurgical intraocular pressure spike, longer residual intracameral bleeding, and a higher risk of reoperation. The aim of this study was to investigate the consequences of clot formation and hyphema in the anterior chamber after internal trabeculotomy. In this retrospective interventional comparative study, we investigated the surgical outcomes of internal trabeculotomy in 142 eyes of 142 patients at Sensho-kai Eye Institute. Concurrent clot formation and L≥2 hyphema (height of hyphema ≥1mm) was observed in 22 eyes. In these cases, the postsurgical IOP was 29.3mmHg at 1 week, significantly higher than the 16.1mmHg in eyes that had L≥2 hyphema but without clot formation ( P =0.0002). However, the 1-week postsurgical IOP in L≥2 hyphema and clot (-) eyes, which measured 16.1mmHg was not significantly greater than that in L<2 hyphema and clot (-) eyes, which measured 18.7mmHg ( P =0.162). Thus, clot formation was identified as a significant factor contributing to high postsurgical IOP at 1 week. The resolution time for anterior chamber bleeding in eyes with concurrent clot formation and L≥2 hyphema was 12.3 days, longer than the 5.8 days observed in L≥2 hyphema eyes without clot formation ( P =0.016). Among the 22 eyes with concurrent L≥2 hyphema and clot formation, 8 required anterior chamber washout. Three of the 10 eyes that underwent washout necessitated additional trabeculectomy, a rate significantly higher than that in nonwashout eyes ( P <0.001). After internal trabeculotomy, the sequelae of concurrent clot formation and L≥2 hyphema in the anterior chamber were more severe than those of simple hyphema without clots. Clot formation negatively affected postoperative IOP.

Optimizing the care management pathway of patients with ischemia and non-obstructive coronary arteries

Ischemia with non-obstructive coronary arteries (INOCA) is defined by the coexistence of anginal symptoms and demonstrable ischemia, with no evidence of obstructive coronary arteries. The underlying mechanism of INOCA is coronary microvascular dysfunction with or without associated vasospasm. INOCA patients have recurrent symptoms, functional limitations, repeated access to the emergency department, impaired quality of life and a higher incidence of cardiovascular events than the general population. Although well described in chronic coronary syndrome guidelines, INOCA remains underdiagnosed in clinical practice because of insufficient awareness, lack of accurate diagnostic tools, and poorly standardized and consistent definitions to diagnose, both invasively and non-invasively, coronary microvascular dysfunction.To disseminate current scientific evidence on INOCA as a distinct clinical entity, during 2022 we conducted at 30 cardiology units all over the country a clinical practice improvement initiative, with the aim of developing uniform and shared management pathways for INOCA patients across different operational settings. The present document highlights the outcomes of this multidisciplinary initiative.

Discrete placental gene expression signatures accompany diabetic disease classifications during pregnancy

Gestational diabetes mellitus (GDM) affects up to 10% of pregnancies and is classified into subtypes GDMA1 (managed by lifestyle modifications) and GDMA2 (requiring medication). However, whether these subtypes are distinct clinical entities or more reflective of an extended spectrum of normal pregnancy endocrine physiology remains unclear. Integrated bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomics harbors the potential to reveal disease gene signatures in subsets of cells and tissue microenvironments. We aimed to combine these high-resolution technologies with rigorous classification of diabetes subtypes in pregnancy. We hypothesized that differences between pre-existing Type 2 and gestational diabetes subtypes would be associated with altered gene expression profiles in specific placental cell populations. In a large case-cohort design, we compared validated cases of GDMA1, GDMA2, and type 2 diabetes (T2DM) to healthy controls by bulk RNA-seq (n=54). Quantitative analyses with RT-qPCR of presumptive genes of significant interest were undertaken in an independent and non-overlapping validation cohort of similarly well-characterized cases and controls (n=122). Additional integrated analyses of term placental single-cell, single-nuclei, and spatial transcriptomics data enabled us to determine the cellular subpopulations and niches that aligned with the GDMA1, GDMA2, and T2DM gene expression signatures at higher resolution and with greater confidence. Dimensional reduction of the bulk RNA-seq data revealed that the most common source of placental gene expression variation was the diabetic disease subtype. Relative to controls, we found 2,052 unique and significantly differentially expressed genes (-2<Log2(fold-change)>2 thresholds; q<0.05 Wald Test) among GDMA1 placental specimens, 267 among GDMA2, and 1,520 among T2DM. Several candidate marker genes (CSH1, PER1, PIK3CB, FOXO1, EGFR, IL2RB, SOD3, DOCK5, and SOGA1) were validated in an independent and non-overlapping validation cohort (q<0.05 Tukey). Functional enrichment revealed the pathways and genes most impacted for each diabetes subtype, and the degree of proximal similarity to other subclassifications. Surprisingly, GDMA1 and T2DM placental signatures were more alike by virtue of increased expression of chromatin remodeling and epigenetic regulation genes, while albumin was the top marker for GDMA2 with increased expression of placental genes in the wound healing pathway. Assessment of these gene signatures in single-cell, single-nuclei, and spatial transcriptomics data revealed high specificity and variability by placental cell and microarchitecture types. For example, at the cellular and spatial (e.g., microarchitectural) levels, distinguishing features were observed in extravillous trophoblasts (GDMA1) and macrophages (GDMA2). Lastly, we utilized these data to train and evaluate four machine learning models to estimate our confidence in predicting the control or diabetes status of placental transcriptome specimens with no available clinical metadata. Consistent with the distinct association of perinatal outcome risk, placentae from GDMA1, GDMA2, and T2DM-affected pregnancies harbor unique gene signatures that can be further distinguished by altered placental cellular subtypes and microarchitectural niches.

Prevalence and Characteristics of Patients with Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease: Overlap Syndrome.

Overlap syndrome (OVS) is a distinct clinical entity that seems to result in potential cardiovascular consequences. We aimed to estimate the prevalence and risk factors for OVS in OSA patients and analyze clinical and PSG characteristics associated with OVS. In this cross-sectional study, 2616 patients evaluated for OSA underwent type-1 polysomnography (PSG). They were grouped as pure OSA (AHI > 15/h) and OVS patients. Demographics, PSG data, pulmonary function tests and arterial blood gases (ABGs) were compared between groups after adjustments for confounders. OSA was diagnosed in 2108 out of 2616 patients. Of those, 398 (19%) had OVS. Independent predictors of OVS were older age [OR: 5.386 (4.153-6.987)], current/former smoking [OR: 11.577 (7.232-18.532)], BMI [OR: 2.901 (2.082-4.044)] and ABG measurements [PaCO2 ≥ 45 OR: 4.648 (3.078-7.019), PO2 [OR: 0.934 (0.920-0.949)], HCO3- [OR: 1.196 (1.133-1.263), all p < 0.001]. OVS was also associated with prevalent hypertension [OR: 1.345 (1.030-1.758), p = 0.03] and cardiovascular disease [OR: 1.617 (1.229-2.126), p < 0.001], depressive symptoms [OR: 1.741 (1.230-2.465), p = 0.002] and nocturia [OR: 1.944 (1.378-2.742), p < 0.001], as well as with indices of OSA severity. Disturbances in sleep architecture were more prominent in OVS expressed by lower %N3 and REM% and higher arousal index. Our data suggest that OVS is prevalent among OSA patients, with distinct clinical and PSG characteristics. These characteristics could be utilized as predictive factors for early identification and further evaluation of these patients towards desirable patient-reported outcomes.