Clinical Grounds Research Articles

Premature Thelarche: An Updated Review.

Premature thelarche is the most common pubertal disorder in girls. The condition should be differentiated from central precocious puberty which may result in early epiphyseal fusion and reduced adult height, necessitating treatment. The purpose of this article is to familiarize physicians with the clinical manifestations of premature thelarche and laboratory tests that may help distinguish premature thelarche from central precocious puberty. A search was conducted in September 2022 in PubMed Clinical Queries using the key term "Premature thelarche". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used to compile the present article. Premature thelarche denotes isolated breast development before the age of 8 years in girls who do not manifest other signs of pubertal development. The condition is especially prevalent during the first two years of life. The majority of cases of premature thelarche are idiopathic. The condition may result from an unsuppressed hypothalamic-pituitary-gonadal axis in the early years of life, an "overactivation" of the hypothalamic-pituitary axis in early childhood secondary to altered sensitivity to steroids of the hypothalamic receptors controlling sexual maturation, increased circulating free estradiol, increased sensitivity of breast tissue to estrogens, and exposure to exogenous estrogens. The cardinal feature of premature thelarche is breast development which occurs without additional signs of pubertal development in girls under 8 years of age. The enlargement may involve only one breast, both breasts asymmetrically, or both breasts symmetrically. The breast size may fluctuate cyclically. The enlarged breast tissue may be transiently tender. There should be no significant changes in the nipples or areolae and no pubic or axillary hair. The vulva, labia majora, labia minora, and vagina remain prepubertal. Affected girls have a childlike body habitus and do not have mature contours. They are of average height and weight. Growth and osseous maturation, the onset of puberty and menarche, and the pattern of adolescent sexual development remain normal. Most cases of premature thelarche can be diagnosed on clinical grounds. Laboratory tests are seldom indicated. No single test can reliably differentiate premature thelarche from precocious puberty. Premature thelarche is benign, and no therapy is necessary apart from parental reassurance. As enlargement of breasts may be the first sign of central precocious puberty, a prolonged follow- up period every 3 to 6 months with close monitoring of other pubertal events and linear growth is indicated in all instances.

Posterior uveal biopsy and the trans-scleral Essen forceps biopsy technique.

Differentiating neoplastic and non-neoplastic uveal tumours can present a diagnostic challenge; intra-ocular biopsy may be necessary. The novel trans-scleral Essen Forceps biopsy (TSEB) technique can improve diagnostic yield compared to fine needle aspiration biopsy (FNAB). We present a case demonstrating the technique and its added value. We also review the success rate of TSEB performed at two tertiary eye centres. Retrospective case report and consecutive case series from August 2021 to March 2023. Inclusion criteria were patients who underwent TSEB of posterior uveal lesions from Moorfields Eye Hospital and Sheffield Teaching Hospitals in the United Kingdom. The outcomes were biopsy success rate and complication rate RESULTS: Eleven biopsies met the inclusion criteria. Eight (73%) were successful, which comprised six uveal melanomas, one melanocytoma and one extranodal marginal zone (ENMZ) lymphoma. One TSEB did not yield tissue for histological examination because of perioperative sample handling. Two (18%) biopsies were histologically inconclusive; both were treated as uveal melanoma on clinical grounds or repeat biopsy. The only complication was vitreous loss and retinal hole without retinal detachment in one eye with a very posterior, shallow choroidal lesion. TSEB is an effective alternative to established biopsy techniques, yielding larger tissue samples than FNAB with intact tissue architecture. We recommend adding TSEB to the armamentarium of the ocular oncologist.

Deciding treatment end point in necrotizing otitis externa: validation of a standardized clinical response assessment strategy with positron emission tomography findings.

Primary: To explore criteria for treatment endpoint in NOE. Secondary: To study correlation of inflammatory markers, Erythrocyte sedimentation Rate (ESR) and C-reactive protein (CRP) with disease status. Prospective cohort study conducted in a tertiary care hospital over two years (2021-2023) consisted 28 patients with NOE. Treatment culmination point was decided based on symptoms control and correlated with PET-scan findings. Clinical response was analysed with respect to the serum inflammatory markers and PET Scan findings. There was fair degree of agreement between clinical resolution and resolution of findings on PET scan (kappa coefficient - 0.76 [95% CI; 0.40,1.00]). Inflammatory markers showed statistically significant decline with clinical resolution but failed to return to normal. Decision to terminate treatment of NOE can be reliably made on clinical grounds in patients remaining asymptomatic for three weeks. Resolution of inflammation on PET scan is in congruity with the clinical remission .

Electroencephalographic source imaging of spikes with concurrent high-frequency oscillations is concordant with the clinical ground truth.

Epilepsy raises critical challenges to accurately localize the epileptogenic zone (EZ) to guide presurgical planning. Previous research has suggested that interictal spikes overlapping with high-frequency oscillations, referred to here as pSpikes, serve as a reliable biomarker for EZ estimation, but there remains a question as to whether and to how pSpikes perform as compared to other types of epileptic spikes. This study aims to address this question by investigating the source imaging capabilities of pSpikes alongside other spike types. A total of 2819 interictal spikes from 76-channel scalp electroencephalography (EEG) were analyzed in a cohort of 24 drug-resistant focal epilepsy patients. All patients received surgical resection, and 16 were declared seizure-free based on at least 1 year of postoperative follow-up. A recently developed electrophysiological source imaging algorithm-fast spatiotemporal iteratively reweighted edge sparsity (FAST-IRES)-was used for source imaging of the detected interictal spikes. The performance of 217 pSpikes was compared with 772 nSpikes (spikes with irregular high-frequency activations), 1830 rSpikes (spikes with no high-frequency activity), and all 2819 aSpikes (all interictal spikes). The localization and extent estimation using pSpikes are concordant with the clinical ground truth; using pSpikes yields the best performance compared with nSpikes, rSpikes, and conventional spike imaging (aSpikes). For multiple spike type seizure-free patients, the mean localization error for pSpike imaging was 6.8 mm, compared with 15.0 mm for aSpikes. The sensitivity, precision, and specificity were .41, .67, and .93 for pSpikes compared with .32, .48, and .93 for aSpikes. These results demonstrate the merits of noninvasive EEG source localization, and that (1) pSpike is a superior biomarker, outperforming conventional spike imaging for the localization of epileptic sources, and especially those with multiple irritative zones; and (2) FAST-IRES provides accurate source estimation that is highly concordant with clinical ground truth, even insituations of single spike analysis with low signal-to-noise ratio.

12605 Two Systematic Reviews Of Treatment Efficacy On Patient Important Outcomes In Children X-linked Hypophosphatemia

Abstract Disclosure: D.S. Ali: None. R. Mirza: None. S. Hussein: None. F. Alsarraf: None. R. Alexander: Consulting Fee; Self; Ultragenyx. Grant Recipient; Self; Ardylex Inc.. H. AbuAlrob: None. M. Brandi: Consulting Fee; Self; Aboca, Alexion, Amolyt, Bruno Farmaceutici, Calcilytix, Echolight, Kyowa Kirin, Personal Genomics,. Speaker; Self; Kyowa Kirin, Abiogen, Alexion, Amgen, Amolyt, Amorphical, Bruno Farmaceutici, Eli Lilly & Company. T.O. Carpenter: Advisory Board Member; Self; Kyowa Kirin, Ultragenyx. Consulting Fee; Self; Kyowa Kirin, Ultragenyx. Grant Recipient; Self; Ultragenyx. Other; Self; Assoc. Editor JBMR, President Ped Endo Soc, Author UpToDate (royalties), XLH-Network (Patient Advisory Org). K. Dandurand: Speaker; Self; Amgen Inc, Kyowa Kirin. G. Filler: Consulting Fee; Self; Kyowa Kirin, Ultragenyx, ProKidney. Speaker; Self; Ultragenyx, ProKidney. P.F. Florenzano: ; Institutional Research Grants: Ultragenyx. ; Advisory Boards: Ultragenyx, Kyowa Kirin. S. Fukumoto: Consulting Fee; Self; Kyowa Kirin. C. Grasemann: Speaker; Self; Kyowa Kirin. E.A. Imel: ; Ultragenyx (Research funding and consulting). ; Kyowa Kirin (research funding and consulting). ; Inozyme (consulting). ; Amgen (research funding). S.M. Jan De Beur: Consulting Fee; Self; Ultragenyx, Kyowa Kirin. Research Investigator; Self; Ultragenyx. E. Morgante: None. L.M. Ward: ; clinical trials with Ultragenyx. ; consultancy to Kyowa Kirin and Ultragenyx. ; unrestricted educational grants from Ultragenyx and Kyowa Kirin (with funds to Dr. Ward’s instituition). A.A. Khan: Advisory Board Member; Self; Amgen Inc, Ascendis, Alexion. Grant Recipient; Self; Takeda, Amolyt, Calcilytix. Speaker; Self; Amgen Inc, Ascendis, Alexion. G. Guyatt: None. Objective: We sought to examine the highest certainty evidence on managing X-linked hypophosphatemia (XLH) in children, aiming to inform treatment recommendations of XLH international guidelines. Data Sources: We searched Embase, MEDLINE, Web of Science, and Cochrane Central from inception to March 2023. We also reviewed reference lists of eligible studies and pertinent review articles. Study eligibility criteria: Eligible studies included randomized controlled trials (RCTs) and observational studies enrolling individuals younger than 18 years old with XLH diagnosed on clinical grounds or with a confirmed pathogenic variant in PHEX. Articles were selected according to specific criteria evaluating the effectiveness of burosumab compared to either no treatment or conventional therapy (phosphate salts and active vitamin D) or evaluating conventional therapy compared to no treatment. Methods: Two reviewers independently determined eligibility, conducted data extraction, and assessed the risk of bias (RoB) in eligible articles. We employed the GRADE methodology to evaluate the certainty of the evidence. Results: After removing duplicates from 7,043 citations, we screened 4,114 records and assessed 254 full texts, of which in the systematic review (SR) addressing burosumab one RCT and one post-Hoc study proved eligible. Being open-label design, the RoB was high, with certainty of evidence on individual outcomes ranging from moderate to very low. Burosumab, compared to conventional therapy, probably prevents lower limb deformity, and improves physical health quality of life (QoL) (moderate certainty). It might also increase height and possibly improve the burden of symptoms related to chronic hypophosphatemia (low certainty). Conversely, burosumab probably increases Treatment-Emergent adverse events after the first administration (moderate certainty), and it may increase dental abscesses (low certainty). In the second SR, one observational study assessing conventional therapy versus no treatment was at high RoB providing very low certainty of evidence regarding the impact of conventional therapy compared to no treatment on final height. Conclusion: Our review indicates that burosumab likely offers benefits in preventing lower limb deformity and improving physical health QoL, while potentially increasing height and improving the burden of symptoms related to chronic hypophosphatemia (low certainty). However, it may also increase adverse events, including dental abscesses. Additionally, our review found limited evidence regarding the impact of conventional therapy compared to no treatment on final height in children. These findings highlight the need for further research to better understand the long-term impact of conventional therapy and burosumab in children. Presentation: 6/2/2024

12589 Two Systematic Reviews Of Treatment Efficacy On Patient Important Outcomes In Adult X-linked Hypophosphatemia

Abstract Disclosure: D.S. Ali: None. R. Mirza: None. F. Alsarraf: None. S. Hussein: None. N. Appelman-Dijkstra: Consulting Fee; Self; Amgen Inc, Kyowa Kirin, UCB. Grant Recipient; Self; Kyowa Kirin. S. Beck-Nielsen: Consulting Fee; Self; Kyowa Kirin, Inozymes, Novo Nordisk. Grant Recipient; Self; Kyowa Kirin. Speaker; Self; Kyowa Kirin. M. Biosse-Duplan: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc.. Grant Recipient; Self; Kyowa Kirin. Speaker; Self; Kyowa Kirin, Alexion Pharmaceuticals, Inc. M. Brandi: Consulting Fee; Self; Alexion Pharmaceuticals, Inc., Aboca, Amolyt, Bruno Farmaceutici, Calcilytix, Kyowa Kirin. Speaker; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Eli Lilly & Company, Takeda, Kyowa Kirin. C. Chaussain: Grant Recipient; Self; Kyowa Kirin. M. Cohen-Solal: Grant Recipient; Self; Kyowa Kirin. Speaker; Self; Kyowa Kirin. R.K. Crowley: Advisory Board Member; Self; UCB, Amgen Inc. Consulting Fee; Self; Kyowa Kirin. Speaker; Self; Kyowa Kirin. K. Dandurand: Speaker; Self; Amgen Inc, Kyowa Kirin. P.F. Florenzano: None. S. Fukumoto: Consulting Fee; Self; Kyowa Kirin. C. Gagnon: Grant Recipient; Self; Takeda, Ascendis Pharma. P. Goodyer: None. C. Grasemann: Speaker; Self; Kyowa Kirin. E.A. Imel: Consulting Fee; Self; Ultragenyx, Kyowa Kirin, Inozyme. Grant Recipient; Self; Ultragenyx, Kyowa Kirin, Amgen Inc. S.M. Jan De Beur: Consulting Fee; Self; Kyowa Kirin, Ultragenyx. E.M. Lewiecki: Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc, Ultragenyx. Speaker; Self; Amgen Inc, Ascendis. E. Morgante: None. L. Ward: Other; Self; Tier 1 (Senior) Research Chair in Pediatric Bone Disorders from the University of Ottawa and the Children’s Hospital of Eastern Ontario Research Institute. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Takeda, Alexion, Ascendis. Grant Recipient; Self; Takeda, Ascendis, Amolyt, Calcilytix. G. Guyatt: None. Objective: Our objective was to examine the highest certainty evidence addressing the management of X-linked hypophosphatemia in adults, aiming to inform treatment recommendations. Eligibility criteria: We searched Embase, MEDLINE, Web of Science, and Cochrane from inception to March 2023 and included RCTs and observational studies enrolling individuals ≥ 18 years diagnosed with XLH on clinical grounds or with a confirmed pathogenic variant in PHEX. Manuscripts evaluating the effectiveness of burosumab compared to either no treatment or conventional therapy (phosphate salts and active vitamin D) or evaluating conventional therapy compared to no treatment were selected. Methods: Two reviewers independently determined eligibility, conducted data extraction, and assessed the risk of bias (RoB). GRADE was used to assess certainty of evidence. Results: After removing duplicates from 7,043 citations, we assessed 254 full texts. Of those, one RCT proved eligible. The RCT of burosumab versus no treatment was at low RoB with certainty of evidence on individual outcomes ranging from high to very low. Burosumab probably improves pain inferred from fracture and pseudofracture healing (moderate certainty); however, burosumab probably has little or no impact on direct pain measures (moderate certainty). While burosumab may reduce the need for parathyroidectomy, indicated by lowered PTH levels (low certainty), it has little or no impact on fatigue (high certainty), stiffness (moderate certainty), and mobility (low certainty) over 24 weeks. Burosumab may also increase dental abscesses (low certainty). No formal comparisons of burosumab and conventional therapy exist; therefore, our low certainty evidence inferences regarding burosumab versus conventional therapy were based on indirect evidence from comparisons of burosumab versus no treatment and from conventional therapy versus no treatment. Observational studies proved at high RoB providing very low certainty of evidence regarding the impact of conventional therapy versus no treatment. This evidence pertained to the reduction in the risk of parathyroidectomy, as well as the reduction in the burden of symptoms caused by chronic hypophosphatemia. Conclusion: Burosumab when compared to no treatment may improve pain through fracture healing and may reduce the need for parathyroidectomy, but it could also increase the risk of dental abscess. However, when using direct measures of pain and function, burosumab demonstrated probably little or no impact on pain and stiffness, little or no impact on fatigue, and may have had little to no impact on mobility. Very low certainty exists regarding conventional therapy versus no treatment in adults. Overall, our review highlights the need for more data to better understand the long-term impact of burosumab and conventional therapy on patient-important outcomes. Presentation: 6/2/2024

Hereditary Hemorrhagic Telangiectasia (Osler's Disease): Systemic, Interdisciplinary, Relatively Common–and Often Missed.

Hereditary hemorrhagic telangiectasia (HHT, Rendu-Osler-Weber disease, or Osler's disease for short) is a systemic disease that can severely impair the quality of life and that requires interdisciplinary treatment. Among rare diseases, it is relatively common, with a prevalence of approximately 1/5000. This review is based on publications retrieved by a selective literature search, including the two international guidelines on clinically relevant aspects of HHT. On average, about two decades elapse between the initial symptoms and the diagnosis of HHT. 95% of patients have nosebleeds; these usually begin before age 20 but can occur at any time, from infancy to old age. The diagnosis is usually made on clinical grounds on the basis of the characteristic telangiectases, a positive family history, and possible involvement of the gastrointestinal tract, lungs, liver, and brain. Nosebleeds can sometimes be reduced by outpatient measures including counseling on keeping the nose moist (expert consensus), self-application of a nasal packing (which improves the quality of life, according to an online survey), and the prescription of tranexamic acid (reduction of nosebleeds from 17.3% [5.5; 27.6] to 54%). In particular, screening (expert consensus) for pulmonary vascular malformations (frequency 10-50%) can prevent many adverse outcomes. If pulmonary vascular malformations cannot be ruled out, antibiotic prophylaxis is recommended before medical procedures that can cause bacteremia (expert consensus). Broad awareness of the condition, early diagnosis, and interdisciplinary treatment improve the quality of life and ultimate outcome of persons with HHT. Nevertheless, there are few options supported by good evidence for the appropriate treatment of this rare, often serious disease.

Gynaecological cancer surveillance for women with Lynch syndrome: systematic review and cost-effectiveness evaluation.

Lynch syndrome is an inherited condition which leads to an increased risk of colorectal, endometrial and ovarian cancer. Risk-reducing surgery is generally recommended to manage the risk of gynaecological cancer once childbearing is completed. The value of gynaecological colonoscopic surveillance as an interim measure or instead of risk-reducing surgery is uncertain. We aimed to determine whether gynaecological surveillance was effective and cost-effective in Lynch syndrome. We conducted systematic reviews of the effectiveness and cost-effectiveness of gynaecological cancer surveillance in Lynch syndrome, as well as a systematic review of health utility values relating to cancer and gynaecological risk reduction. Study identification included bibliographic database searching and citation chasing (searches updated 3 August 2021). Screening and assessment of eligibility for inclusion were conducted by independent researchers. Outcomes were prespecified and were informed by clinical experts and patient involvement. Data extraction and quality appraisal were conducted and results were synthesised narratively. We also developed a whole-disease economic model for Lynch syndrome using discrete event simulation methodology, including natural history components for colorectal, endometrial and ovarian cancer, and we used this model to conduct a cost-utility analysis of gynaecological risk management strategies, including surveillance, risk-reducing surgery and doing nothing. We found 30 studies in the review of clinical effectiveness, of which 20 were non-comparative (single-arm) studies. There were no high-quality studies providing precise outcome estimates at low risk of bias. There is some evidence that mortality rate is higher for surveillance than for risk-reducing surgery but mortality is also higher for no surveillance than for surveillance. Some asymptomatic cancers were detected through surveillance but some cancers were also missed. There was a wide range of pain experiences, including some individuals feeling no pain and some feeling severe pain. The use of pain relief (e.g. ibuprofen) was common, and some women underwent general anaesthetic for surveillance. Existing economic evaluations clearly found that risk-reducing surgery leads to the best lifetime health (measured using quality-adjusted life-years) and is cost-effective, while surveillance is not cost-effective in comparison. Our economic evaluation found that a strategy of surveillance alone or offering surveillance and risk-reducing surgery was cost-effective, except for path_PMS2 Lynch syndrome. Offering only risk-reducing surgery was less effective than offering surveillance with or without surgery. Firm conclusions about clinical effectiveness could not be reached because of the lack of high-quality research. We did not assume that women would immediately take up risk-reducing surgery if offered, and it is possible that risk-reducing surgery would be more effective and cost-effective if it was taken up when offered. There is insufficient evidence to recommend for or against gynaecological cancer surveillance in Lynch syndrome on clinical grounds, but modelling suggests that surveillance could be cost-effective. Further research is needed but it must be rigorously designed and well reported to be of benefit. This study is registered as PROSPERO CRD42020171098. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129713) and is published in full in Health Technology Assessment; Vol. 28, No. 41. See the NIHR Funding and Awards website for further award information.

A rare case of trigeminal trophic syndrome with periorbital cellulitis and full-thickness upper eyelid defect in an undiagnosed patient with human immunodeficiency virus: a case report

BackgroundTrigeminal trophic syndrome is a rare cranial and facial condition caused by damage to the central or peripheral branches of the trigeminal nerve. This syndrome consists of a triad of anesthesia, paresthesia, and crescent-shaped facial ulcer involving the ala nasi and sometimes extending to the upper lip. Although previous screening for human immunodeficiency virus in some patients with trigeminal trophic syndrome was negative, we present a unique case of trigeminal trophic syndrome who tested positive for human immunodeficiency virus with eye complications.Case presentationWe present a rare case of trigeminal trophic syndrome in a 44-year-old Black African woman who tested positive for human immunodeficiency virus. She presented with a 6-week history of progressive, persistent, and painless left sided facial and scalp ulcerations that started as small skin erosion. Diagnosis of trigeminal trophic syndrome was made on clinical grounds based on the triad of anesthesia, paresthesia, and unilateral crescent-shaped ulcer in the trigeminal dermatome and her past medical history. The ulcer healed completely after counseling and pharmacological therapy, but she later developed left periorbital cellulitis and left upper eyelid full-thickness defect.ConclusionThis is by far the first documented case of trigeminal trophic syndrome with a positive human immunodeficiency virus test. Testing for human immunodeficiency virus in patients with trigeminal trophic syndrome is necessary as this can help improve clinical management and treatment outcomes. Seeking the services of specialists remotely in resource constraint settings is beneficial for managing complications associated with trigeminal trophic syndrome.

BACTERIOLOGICAL PROFILE AND ANTIMICROBIAL SUSCEPTIBILITY PATTERN OF SURGICAL SITE INFECTIONS IN A TEACHING HOSPITAL

Objective: Surgical site infections (SSI) are defined as infections occurring within 30 or 90 d after surgical operation or within 1 y, if an implant is left in place after procedure and affecting either incision or deep tissues at the operation site. SSI is one of the quality indicators of the healthcare system. Due to advent of newer antibiotics and emergence of multidrug-resistant bacteria, SSI requires reappraisal of the microbiological flora and in vitro antibiotic sensitivity pattern. The aim of the present study is to determine the incidence etiology of SSI, and determine their Antibiogram. Methods: Cross-sectional study conducted for a period of three months from January 2024 to March 2024. A total of fifty swabs/pus specimens from various types of surgical sites suspected to be infected on clinical grounds were collected from the post-operative wards of surgical departments and processed in Microbiology laboratory. Isolation and identification of bacterial agents were done as per standard protocols. Antimicrobial susceptibility testing was performed by Kirby-Bauer’s disc diffusion method. Results: Out of 50 samples, 32 were culture-positive. 87.50% showed monomicrobial growth and 12.50% showed polymicrobial growth. Analysis of bacterial profile shows Staphylococcus aureus (27.77%) was the predominant isolate, followed by Pseudomonas aeruginosa (19.44%) and Escherichia coli (19.44%). Antibiogram of gram-positive isolates showed sensitivity to Teicoplanin, Vancomycin, and linezolid, whereas gram-negative isolates were sensitive to Meropenem, Piperacillin-tazobactam and levofloxacin. Conclusion: Status of SSI is the main quality indicators of hospital infection control and prevention measures. Continuous surveillance on etiology and antibiogram of SSI is necessary to monitor antimicrobial resistance and guide in empirical treatment.

Low rates of complications and β-lactam resistance in viridans group streptococci bloodstream infection among cancer patients receiving chemotherapy.

Viridans group streptococci (VGS) bloodstream infection (BSI) frequently occurs in cancer patients receiving chemotherapy, and is associated with infective endocarditis (IE) in up to 20% of cases in the general population. In cancer patients receiving chemotherapy with VGS BSI, we aimed to: (i) determine the incidence of infective complications including IE, (ii) assess the utility of echocardiography in this patient population, (iii) determine the duration and type of antimicrobial therapy received for monomicrobial infections, and (iv) determine the evolution of antimicrobial resistance. VGS BSIs (excluding Streptococcus pneumoniae and Streptococcus pseudopneumoniae) in cancer patients receiving chemotherapy were identified from a statewide public pathology database between 2013 and 2022 at our tertiary centre. Medical records were accessed for clinical, microbiological and radiological data. Of 581 patient episodes screened, 183 episodes involving 171 patients met inclusion criteria. Of these, 51% were bone marrow transplantation (BMT) patients, 40% were non-BMT haematology patients, and 8% were solid organ malignancy patients. The median age was 55 years, and 96% were neutropenic at the time of blood culture collection. A transthoracic echocardiogram was performed for 71% of episodes, and one patient met modified Duke's criteria for definite IE, although this diagnosis was not suspected on clinical grounds. Other complications were uncommon. Benzylpenicillin resistance was rare (2.9%) and did not change over time. Most episodes (75%) were treated with piperacillin/tazobactam. For monomicrobial BSIs, the median antibiotic duration was 5 days (IQR 2-7) post-neutropenia resolution. Infective complications and antimicrobial resistance are rare in cancer patients with VGS BSI. This may provide a safe opportunity to limit both investigations (e.g. echocardiogram) and prolonged exposure to broad-spectrum antimicrobials.

Lateral rectus palsy as the first presentation of Kikuchi Fujimoto’s disease

Kikuchi Fujimoto’s Disease (KFD) or histiocytic necrotising lymphadenitis is recognised as a disease with a benign and indolent course. The common clinical symptoms of KFD include fever, headache, arthralgia and cervical lymphadenopathy. The diagnosis is based on clinical grounds and histological findings of lymph node biopsy. Kikuchi disease presenting with neurological manifestations is seldom seen. Out of all reported neurological manifestations, aseptic meningitis, brainstem encephalitis and cerebellar ataxia are common. We report a case of a 16 year old girl presenting with right sided lateral rectus palsy as the first presentation of KFD.

Pulse Therapy in Rituximab Era: A Retrospective Study of 124 Patients of Pemphigus from a Tertiary Care Center of South Rajasthan

Abstract Background: Pemphigus is a potentially life-threatening autoimmune blistering disease which characteristically affects skin and mucosae. Pulse therapy for the treatment of pemphigus has been in vogue for several years and considered better than conventional corticosteroids. Aims and objectives: This study was conducted to evaluate the efficacy and safety of pulse therapy in pemphigus patients treated over a period of 10 years. Materials and Methods: This retrospective study was based on medical records of Pemphigus patients treated at Department of Dermatology from January 2008 to December 2017. Diagnosis of pemphigus was made on clinical ground, Tzanck smear and histopathology of skin/mucous membrane lesions. Patients were put on DCP/DAP depending on the completion of family. Results: A total of 124 patients were included in the study. Age of patients ranged from 18 years to 72 years with mean of 41.21±12.71 years. Amongst 124 patients, 114 (92%) had pemphigus vulgaris and 10 (8%) had pemphigus foliaceous. 89 patients received DCP and 35 patients received DAP therapy. Number of pulses received by patients in phase I ranged from 4 to 27, average being 8.16±4.63. 106 patients completed the phase I of which 83 completed the phase II. 54 patients had successfully completed phase III of which 22 are currently in phase IV and 28 patients have completed their five year follow up period and considered as cured. Conclusion: Pulse therapy is a cheap and easily available mode of therapy in treatment of pemphigus in India even in the present era of modern molecules like Rituximab. With pulse therapy, it is now possible to induce and maintain remission, and achieve cure, provided the patients strictly adhere to the prescribed schedule.

Clear Aligner Therapy Concerns: Addressing Discrepancies Between Digitally Anticipated Outcomes and Clinical Ground Realities.

Expeditious strides in the fields of biomaterials, computer-aided design, and manufacturing have catapulted clear aligner therapy (CAT) to become a comprehensive orthodontic treatment modality. The efficiency of achieving planned tooth movement with clear aligners is a significant consideration while setting up the final treatment goals, as well as calculating treatment times and costs based on the available evidence. Contemporary research outcomes confirm that one of the most commonly reported clinical concerns with CAT is the discrepancy between the prescribed outcome in the digital treatment plan and the clinically achieved outcome from a given series of aligners. Inaccurate prediction of tooth movements may not only lead to a prolonged duration of aligner treatment with an additional need for refinement strategies; but it may also cause other concerns, such as patient burnout and increased potential for relapse. The authors of this paper have elucidated some of the critical elements that may help address this discrepancy between digitally prescribed and clinical outcomes based on an evidence-based approach with regard to the predictability and accuracy of CAT. A strong diagnostic acumen, judicious case selection, solid biomechanical understanding of various types of orthodontic tooth movements, a research framework that keeps pace with technological and material developments and provides evidence-based knowledge of the limitations of CAT; and above all, the ability of the clinician to continually innovate as per different clinical scenarios, all contribute to attaining treatment predictability, efficacy, and efficiency with CAT.

Hereditary Gastrointestinal Tumor Syndromes: When Risk Comes with Your Genes.

Despite recent campaigns for screening and the latest advances in cancer therapy and molecular biology, gastrointestinal (GI) neoplasms remain among the most frequent and lethal human tumors. Most GI neoplasms are sporadic, but there are some well-known familial syndromes associated with a significant risk of developing both benign and malignant GI tumors. Although some of these entities were described more than a century ago based on clinical grounds, the increasing molecular information obtained with high-throughput techniques has shed light on the pathogenesis of several of them. The vast amount of information gained from next-generation sequencing has led to the identification of some high-risk genetic variants, although others remain to be discovered. The opportunity for genetic assessment and counseling in these families has dramatically changed the management of these syndromes, though it has also resulted in significant psychological distress for the affected patients, especially those with indeterminate variants. Herein, we aim to summarize the most relevant hereditary cancer syndromes involving the stomach and colon, with an emphasis on new molecular findings, novel entities, and recent changes in the management of these patients.

Challenges in clinical diagnosis of Clade I Mpox: Highlighting the need for enhanced diagnostic approaches.

Due to limited diagnostic capacity and availability of point-of-care tests, diagnosis of Clade I mpox in the geographical regions most affected is usually on clinical grounds. This may be complicated due to the similarity between mpox and varicella (chickenpox) lesions. Visual assessment of lesions is also used for determining clinical progress and to assess patient outcomes in clinical trials. However, there has been no investigation into whether clinicians can (i) identify Clade I mpox compared to other viral lesions (ii) differentiate between Clade I mpox lesion stages. The objective of this study was to evaluate inter-rater reliability and agreement between clinicians assessing lesions in patients with Clade I mpox. We presented experienced clinicians with 17 images of Clade I mpox or varicella and asked them to independently indicate the most likely diagnosis-mpox or varicella-and to categorise the lesions according to their stage. When selecting the most likely diagnosis, accuracy varied across all images, the inter-rater reliability was poor (κ = 0.223; z = 10.1) and agreement was moderate (Po = 68%). When categorising lesions according to their type, if a single lesion type was present in the image, inter-rater reliability was moderate (κ = 0.671, z = 40.6) and agreement was good (Po = 78%), but when multiple lesion types were shown in an image, both inter-rater reliability (κ = 0.153, z = 10.5) and agreement (Po = 29%) decreased substantially. This study demonstrates that there are presently limitations in using visual assessment to diagnose Clade I mpox and evaluate lesion stage and treatment outcomes, which have an impact on clinical practice, public health and clinical trials. More robust indicators and tools are required to inform clinical, public-health, and research priorities, but these must be implementable in countries affected by mpox.

Controversies in the management of community-acquired pneumonia in adults.

Community-acquired pneumonia (CAP) is a common infectious syndrome in Australia and a leading global cause of morbidity and mortality. It drives a significant amount of antimicrobial prescribing in Australia. Accurate assessment and stratification of CAP severity is important. However, adequate evaluation is challenging and controversy remains about the optimal method. Streptococcus pneumoniae is the most commonly identified bacterial pathogen causing CAP. As such, oral amoxicillin monotherapy is the mainstay of empirical therapy for low-severity CAP. The need to start empirical therapy for pathogens such as Mycoplasma pneumoniae and Legionella species in low-severity CAP remains controversial; evaluating the causative pathogen on clinical grounds alone is difficult. Oral antibiotics recommended for CAP (e.g. amoxicillin, doxycycline) have excellent bioavailability and may be used instead of intravenous therapy in some hospitalised patients. A duration of 5 days of antibiotic therapy is recommended in clinical practice guidelines for patients with uncomplicated CAP who meet stability criteria at follow-up.

Cost-effectiveness of one-stop-shop [18F]Fluorocholine PET/CT to localise parathyroid adenomas in patients suffering from primary hyperparathyroidism.

We conducted a cost-effectiveness analysis in which we compared a preoperative [18F]Fluorocholine PET/CT-based one-stop-shop imaging strategy with current best practice in which [18F]Fluorocholine PET/CT is only recommended after negative or inconclusive [99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT for patients suffering from primary hyperparathyroidism. We investigated whether the one-stop-shop strategy performs as well as current best practice but at lower costs. We developed a cohort-level state transition model to evaluate both imaging strategies respecting an intraoperative parathyroid hormone monitored treatment setting as well as a traditional treatment setting. The model reflects patients' hospital journeys after biochemically diagnosed primary hyperparathyroidism. A cycle length of twelve months and a lifetime horizon were used. We conducted probabilistic analyses simulating 50,000 cohorts to assess joint parameter uncertainty. The incremental net monetary benefit and cost for each quality-adjusted life year were estimated. Furthermore, threshold analyses regarding the tariff of [18F]Fluorocholine PET/CT and the sensitivity of [99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT were performed. The simulated long-term health effects and costs were similar for both imaging strategies. Accordingly, there was no incremental net monetary benefit and the one-stop-shop strategy did not result in lower costs. These results applied to both treatment settings. The threshold analysis indicated that a tariff of €885 for [18F]Fluorocholine PET/CT was required to be cost-effective compared to current best practice. Both preoperative imaging strategies can be used interchangeably. Daily clinical practice grounds such as available local resources and patient preferences should inform policy-making on whether a hospital should implement the one-stop-shop imaging strategy.

INVESTIGACIÓN BIOMÉDICA EN CHILE: APRENDIZAJE EN 48 AÑOS DE DIÁLOGO CON LAS PLAQUETAS

Biomedical research in Chile is necessary, it positions us at the limit of knowledge and improves the quality, accreditation and ranking of the academic institutions where it is developed. Its financing requires the political commitment regarding its importance for our country and of academic institutions to create a protective microenvironment for its flourishment. Private companies have consistently increased their contribution to R&D, but understandably, with a smaller presence in biomedicine. Specific competencies of the investigators may be highly useful and decisions regarding introduction of new products and technologies in clinical and laboratory grounds. Despite the remoteness of the major research centers, our work will be relevant if we overcome our objective limitations with creativity and extra effort. These include available resources, considering that the fraction of GDP budget for R&Din OCDE countries is 8 times higher than ours; proficiency in English language is a major problem for many of us; establishing trusting relationships with leading researchers in the field is a pre-requisite to grant our insertion in major scientific societies and for creating international collaborations; eagerly evaluate and use the transiently open windows for research; use the benefits of comparative advantages or unique conditions in Chile that enhance the originality of our studies; as phy­sicians, we have privileged access to patients for descriptive or mechanistic studies, including technical advantages, lower cost, and higher appraisal in scientific journals. We will expand on these considerations in our presentation.

#2265 The challenge of renal biopsy in diabetic patients: evaluation of a single center large cohort from North-West Italy

Abstract Background and Aims Diabetic kidney disease is one of the most severe long-term complications of diabetes. Currently, the international guidelines suggest diagnosis of diabetic nephropathy to be achieved on a clinical ground only. However, in the heterogeneous cluster of different conditions putatively co-existing with diabetes, renal biopsy is a unique tool for an accurate diagnosis and a guide for patient management. The aim of the study was to retrospectively analyze monocentric case history of kidney biopsies performed in diabetic patients over a period of 10 years. Patient's data were collected both at the time of histological examination and during follow-up. Method Data of renal biopsies (RB) performed in patients with diabetes mellitus from 1st January 2014 to 31th July 2023, were collected. Patient identification was performed by reviewing clinical histories and histopathological charts. Data on the indication for RB were collected from the medical report of the hospitalisation when the procedure was performed or from the visit when the indication was given. Atypical features were categorized according to an adaptation of the 2007 KDOQI guidelines for diabetes and chronic kidney disease. The significance of baseline differences was determined by the chi-squared test, Fisher's exact test or the unpaired t-test, as appropriate. Significance of univariate analysis were confirmed through the use of multivariate analysis. Correlation analysis, linear regression and Cox regression were also performed. A two-sided P-value <0.05 was statistically significant. All statistical analyses were performed using SPSS version 26.0 (IBM, Armonk, NY, USA). Results Among 1990 patients (pts) who underwent kidney biopsy during the study period, 297 had type 1 or type 2 DM (14.9%) and were therefore included in the study, regardless of diagnostic suspicion and histological findings. Histological examination revealed diabetic nephropathy (DN) in 112 cases (group 1), DN associated with another kidney disease in 56 cases (group 2) and nondiabetic renal diseases alone in the remaining 129 cases (62%) (group 3). In group 2 the kidney disease most frequently associated with DN was focal and segmental glomerulosclerosis, FSGS (24/56 pts) followed by IgA nephropathy, IgAN (14/56 pts). In this population the histological examination led to specific therapeutic indications in 22 patients. In group 3 the most frequently observed kidney disease was FSGS (37/112 pts) followed by ANCA-vasculitis (14/112 pts), membranous nephropathy (14/112 pts) and IgAN (10/112). In this population, histological examination led to a specific therapeutic indication in 67 pts. To determine predictors for histopathological diagnosis of DKD, we ran a logistic regression model. The covariates used in this model were the duration of diabetes, presence of retinopathy, hypertension, serum creatinine values, eGFR values and 24-hours proteinuria. None of them was found to be statistically significant. It should also be noted that 47 out of 112 pts (42%) with diabetic nephropathy had no retinopathy. In contrast, 9 pts (7%) with histological evidence of NDRD had diabetic retinopathy. 215 out of 297 pts had a follow-up of at least 6 months. During a mean follow up of 41.6±31.8 months, 53 pts (24 in group 1, 15 in group 2 and 14 in group 3) reached end stage kidney disease (16.5 months). In our population the presence of DN associated with another biopsy-proven nephropathy was especially prevalent. Having double nephropathy conferred a relative risk-RR for dialysis of 1.8089 (95% CI 1.0094 to 3.2415, P = .0464). Conclusion To our knowledge this is the largest cohorts of diabetic patients receiving renal biopsy even reported in a Western country. Our data proved kidney biopsy not to be an academic exercise in diabetic pts. Clinical and laboratory features do not predict histologic findings. Renal biopsy allowed the identification of unsuspecting nondiabetic kidney injuries and double nephropathies, which could be susceptible to different outcomes, and paved the pathway for treatment of potentially manageable histological changes.