bluuebunny/crossref_metadata_2025 huggingface dataset:
Susceptibility to insulin resistance in indigenous Australians may be down stream of resistin.
Authors: Good David A. , Cardinal John , Ware Robert S. , Marks Lisa , Kesting Janine B. , Chan Lionel C.K. , Shaw Joanne T.E.
Published: August 2024

Obesity is thought to be a major risk factor for the development of insulin resistance and type 2 diabetes mellitus. However, not all obese or insulin resistant individuals develop T2DM suggesting additional factors are required to cause disease. In order to identify additional mechanisms leading to insulin resistance and T2DM, we measured plasma adipokines as well as established biochemical risk factors for developing T2DM in a large indigenous Australian family. Results: We found T2DM individuals had higher insulin resistance (as measured by HOMA-IR) (p< 0.001), triglyceride (p= 0.003), cholesterol (p=0.02) and TNFα (p=0.03) levels than normoglycaemic controls, independent of age, gender and BMI. The alterations in insulin resistance could not be attributed to TNFα, as we did not find a correlation between TNFα and HOMA-IR in either normoglycaemic or T2DM individuals. In contrast, resistin correlated strongly to HOMA-IR in T2DM (P<0.001) but not normoglycaemic individuals despite the lack of significant differences in circulating levels. We also showed obese T2DM individuals had significantly lower leptin levels (P<0.001) and ß cell function (as measured by HOMA-%B) (P<0.001) compared to obese normoglycaemic family members. Conclusion: These results suggest that events downstream of resistin signalling warrant further investigation to identify the cause for increased susceptibility to insulin resistance in this family. The lower leptin levels in obese T2DM individuals may be explained by a reduced ß cell function. Longitudinal studies are required to assess the utility of TNFα and leptin levels in relation to BMI as risk factors for T2DM.
Effects of iloprost (a prostacyclin analogue) on the endothelial dysfunction and foot ulcers in diabetic patients with peripheral arterial disease
Authors: Sert Murat , Soydas Baris. , Aikimbaev Kairgeldy , Tetiker Tamer
Published: August 2024

Objectives: To asses the efficiency of iloprost (an analogue of prostacyclin) infusion on endothelial functions and amputation rate in diabetic foot ulcers with complicated macroangiopathy. Material and Methods: Sixty (36 men / 24 women) type 2 diabetic patients (61.8 ± 9.7 years, mean ±SD) with diabetic foot ulcer and peripheral arterial occlusive disease, stage III or more by Wagner classification, and 15 (9 male/ 6 female) healthy controls (60.7 ± 9.1 years, mean ±SD) were enrolled in the study. Thirty patients (group I) had iloprost infusion (0.5-2 ng/kg/min for 6 h) for 10 consecutive days. Endothelial functions were determined by brachial arterial flow mediated dilation (FMD) method at stage 0 (basal), 10th and 30th days. Group II patients (n=30) were treated in the same manner as group I except iloprost treatment constituting a patient control group. Results: Group I patients showed a significant improvement in the endothelial functions at 10th day, and 30th day (p=0.002) in respect to group II . There were no differences between group I and group II regarding the hospitalization period and amputation rates. Iloprost was well tolerated. Three patients had adverse reactions such as maculo-papular skin eruptions, itching, hypotension and dyspnea due to iloprost infusion; one completed the treatment and 2 had to discontinue the iloprost infusion. Conclusion: Ten-day iloprost infusion therapy to patients with diabetic foot ulcers seems to be efficient in the improvement of endothelial function, but, despite our positive clinical observation, this improvement does not affect the outcome of the amputation rates at 30 days follow up period.
Effect of Nigella Sativa oil on various clinical and biochemical parameters of metabolic syndrome
Authors: Najmi A. , Haque S.F. , Naseeruddin M. , Khan R.A.
Published: August 2024

Background: The seeds of Nigella sativa plant have been used to promote health and fight disease for centuries especially in the Middle East and Southeast Asia. This plant has been a great focus of research. This clinical study was undertaken to determine the adjuvant effect of Nigella sativa oil on various clinical and biochemical parameters of the metabolic syndrome. Methodology: This prospective study was conducted at a tertiary health care centre in North India. After final diagnosis and considering inclusion and exclusion criteria, sixty patients were enrolled in this study. Informed and written consent was taken from all the patients enrolled. Approval from institutional ethical committee was obtained. Patients were divided into two groups of thirty. In group I (standard group) patients were given tablet Atorvastatin 10 mg once a day and tablet Metformin 500 mg twice a day for a period of six weeks. In group II (Nigella sativa) group, patients were given tablet Atorvastatin 10 mg once a day, tablet Metformin 500 mg twice a day and Nigella sativa oil 2.5 ml twice daily for a period of six weeks. Blood sugar, both fasting and postprandial, fasting lipid profile, body mass index, body weight and waist circumference were recorded before and after completion of therapy. Result: The above mentioned methodology was followed and it was found that the difference in percentage improvement in group II was significant with reference to total cholesterol, low density lipoprotein (LDL) and fasting blood glucose (P<0.05). Conclusion: Nigella sativa oil is effective as an add-on therapy in patients with metabolic syndrome. Nigella sativa oil has a significant therapeutic activity in diabetic and dyslipidemic patients.
Effects of progressive resistance training and aerobic exercise on type 2 diabetics in Indian population
Authors: Shenoy Shweta , Arora Ekta , Jaspal Sandhu
Published: August 2024

Background and objective: The Indian population faces a high risk for diabetes because of a high genetic predisposition and susceptibility to environmental insults. The objective of this study was to evaluate the effects of 16 weeks of Progressive resistance training (PRT) and Aerobic exercise (AE) on glycemic control, blood pressure, heart rate, muscle strength and control of type 2 diabetics. Materials and Methods: A total of 30 type 2 diabetics, 14 females and 16 males, aged between 40-70 years, were randomly assigned to the 16 weeks supervised PRT (n=10), or AE (n=10) or Control group (n=10). Pre- and post-outcome measures included glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), blood pressure (BP), heart rate (HR) and isometric muscle strength of the right hamstring and quadriceps muscles. Results: Plasma glycosylated hemoglobin levels decreased significantly (p=0.002) both in the PRT (7.57 ± 1.4 to 5.74 ± 0.8) and in AE group (8.11 ± 0.9 to 6.78 ± 1.3). FBG decreased by 39.9% in PRT group by14.3% in AE group and by 18.6% in the control group. PRT group exhibited significant reductions in blood pressure (p=0.002 for systolic BP, p<0.001 for diastolic BP) and heart rate (p=0.007). Improvements in isometric muscle strength and balance were seen in both exercise groups. Conclusion: PRT is a more effective form of exercise training than AE for improving glycemic control, blood pressure and heart rate in type 2 diabetics.
The effect of lifestyle practices on blood glucose levels and the development of diabetic complications in women diagnosed with type II diabetes mellitus in Guyana
Authors: Cummings E. , Castang S. , Persaud R. , Seepersaud R. , Seepersaud H. , Raja V. , Defreitas A. , Adeghate E. , Singh J.
Published: August 2024

Type 2 diabetes mellitus (T2DM) is a major health problem in Guyana especially among women. This study evaluated the effects of lifestyle habits on blood glucose control and the development of complications in T2DM female patients. A pretested questionnaire was administered to a total of 39 women between the ages of 44 to 65 years who were previously diagnosed with T2DM for a period of no less than 5 years at the West Demerara Regional Hospital Diabetic Clinic. The patients were divided into two groups, those who adhered to healthy lifestyle habits (group 1) based on body mass index (BMI) and those who did not (group 2). Information for each group was based on lifestyle practices, fasting blood glucose (FBS), random blood glucose (RBS) and diabetic complications. The results show that the mean RBS and FBS values for patients who practised “healthy lifestyle habits” were significantly (P<0.05) lower when compared to those who practised “unhealthy lifestyle habits”. A significant majority of these patients also controlled their blood glucose with the use of one medication when compared to group 2 patients who had unhealthy lifestyle habits and who also needed two or more medications to treat their diabetes. Patients in group 1 who controlled their blood glucose levels and adhered to healthy life style habits had less diabetic complications. It was concluded that patients who adapted healthy lifestyle practices had lower mean RBS and FBS levels when compared to those who did not. These patients also had lower BMI and showed a reduced risk for the development of diabetic-induced long term complications. It can be concluded that a healthy diet and regular exercise are the mainstay therapy for patients with T2DM and to achieve this, the patients must adhere to life style changes to enjoy a better quality of life.
An evaluative study of auditory brain-stem evoked response patterns in diabetic subjects with normal hearing
Authors: Alam Md. Noorain , Jalvi Rajeev , Rangasayee R. , Katarkar Ashish , Jain A. Anil
Published: August 2024

Hearing impairment is a late complication of diabetes mellitus (DM). The present study was needed considering high incidence of diabetes in Indian population and its complications in the form of hearing loss. Delay in the neural conductance along the auditory pathway due to DM was assessed by means of Auditory Brainstem Response (ABR). The sample comprised of three groups, first group comprising of normal healthy 16 ears, the second group with type 1 DM and the third group with type 2 DM comprising of 16 ears each, respectively. ABR recordings showed that absolute latencies of waves I, III, and V that were significantly prolonged in the diabetic group compared to control (P<0.05). However, when two diabetic groups were compared with each other, the difference between latencies of waves I, V in the two diabetic groups was statistically significant (P<0.05). With increase of stimulus presentation rate from 20/s to 72/s in type 2 DM, there was a significant delay in absolute latencies of wave I, III, V as well as interpeak latencies of waves III-V, and I-V. There is a delay in neural conductance due to DM which can be measured using ABR even before manifestation of actual hearing loss.The prolongation of latency of ABR in diabetic patients should raise concern about damage to the auditory nerve. A close follow up will be required in these patients.
Erythrocyte ATPase activity in relation to hyperglycemia and hyperlipidemia in diabetic urban Indian population
Authors: Nirala Bikesh K. , Saluja Shelza , Mishra Anoop , Gohil Nivedita K.
Published: August 2024

This study examines the relationship between; erythrocyte membrane bound Na+K+- ATPase activity, HbA1c level, Hb-AGE (hemoglobin advanced glycation end product) level and lipid profile in Indian diabetic population. The aim was to look at the dependence of this parameter on glycemic and lipid indices in general. Control subjects were volunteers with no diabetic history but were either normolipidemic or dyslipidemic. The diabetic patients were categorized on the basis of glycemic control (HbA1c values) and further into normolipidemic or dyslipidemic groups. HbA1c was analyzed by affinity chromatography while all other parameters including hemoglobin, plasma glucose and lipid profile was estimated using kits on automated analyzer. Hb-AGE was measured in terms of fluorescence intensity and RBC-ATPase activity was measured using an assay kit. Among the diabetic groups, patients in the uncontrolled category (Group 3) were maximally dyslipidemic with high total cholesterol (TC) and triglyceride levels (TG). Observations indicate that even though HbA1c is not significantly different between dyslipidemic and normolipidemic patients in each group, levels of fasting blood sugar, TG and LDL cholesterol were significantly higher in the former. Na+-K+ATPase activity was found to decrease as a function of HbA1c in an inverse manner but did not show any significant correlation with TC levels. Our data indicates that erythrocyte membrane Na+-K+ATPase activity is significantly related to glycemic status rather than to the lipidemic status of individuals in the Asian Indian population. Glycation of the membrane proteins rather than increase in membrane cholesterol content alters the enzyme function.
Effects of inulin fibre Supplementation on Serum Glucose and Lipid Concentration in Patients with Type 2 Diabetes
Authors: Bonsu Nana K.A. , Johnson Shanthi
Published: August 2024

Individuals who develop type 2 diabetes increase their chances of developing other health concerns such as cardiovascular disease. Soluble fibre has been shown to have positive effects on serum lipid and glucose levels. Inulin is a type of soluble fibre whose effects on serum lipid and glucose levels in individuals with type 2 diabetes are inconclusive due to the few studies that have been conducted. This study examined the effects of daily intake of 10 g of inulin-based fibre. This study included 36 individuals diagnosed with type 2 diabetes. Using a randomized, double-blind design patients consumed 10 g of either an inulin fibre supplement or xylitol as a placebo for 12-weeks. Compliance, expressed as the proportion of supplements not returned, was near 100% for both treatments. Inulin supplementation did not significantly affect fasting concentrations of serum total cholesterol, HDL cholesterol, LDL cholesterol, serum triglycerides, serum glucose, or hemoglobin A1c values. These results indicate that daily consumption of 10 g of inulin for 12 weeks does not affect serum lipid and glucose levels in patients with type 2 diabetes.The significant finding(s) of the Study: Short term supplementation of inulin is not effective in changing serum glucose and lipid profiles among those with type 2 diabetes.The study adds: Inulin supplementation on a short term may not be needed or effective in changing serum glucose and lipid profiles among individuals with well managed diabetes.
Photobiomodulation of surgical wound dehiscence in diabetic individuals by low level laser therapy following median sternotomy: A case series
Authors: Dixit Snehil , Maiya Arun , Umakanth Shashikiran , Borkar Shirish
Published: August 2024

In this single case study we attempt to outline the possible effect of low level laser therapy on delayed wound healing (LLLT) in chronic dehiscent sternotomy of a diabetic individual. The methods that were employed to evaluate changes pre and post irradiation were wound photography, wound area measurement, pressure ulcer scale of healing (PUSH) and visual analogue scale (VAS) for pain. After irradiation, proliferation of healthy granulation tissue was observed with decrease in scores of PUSH for sternal dehiscence and VAS for bilateral shoulders and sternal dehiscence. We found that LLLT irradiation could be a novel method of treatment for chronic sternal dehiscence following coronary artery bypass grafting (CABG), as it augments wound healing with an early closure of the wound deficit.
The Impact of Digital Transformation on Blood Donation and Donor Characteristics
Authors: Niklas Norbert , Loimayr Claudia , Lenz Julia , Süßner Susanne , Schuster Gerhard , Jungwirth David , Watzinger Werner , Federsel Stephan
Published: August 2024

Introduction: The management of an adequate donor pool is a constant and challenging task for blood centers in order to provide blood supply. New methods are required to streamline processes and attract (new) donors on a sustained basis. We present a digitalization method without media disruption and show the impact on our donors and their behavior. Methods: We designed and created a blood donation app that is fully compliant to all regulations and conforms to donor expectations. The presented digitalization serves the donor from preparation before the donation (health questionnaire) until completion of laboratory testing (medical report). Many other features are included and continuously attract donors to engage with the blood donation topic. Results: Eighteen months after the launch of our app, there are already 45,000 users. The digital questionnaire reduced the number of deferrals by 31.9% compared to the conventional paper questionnaire. Digital adopters show a significantly shorter donation interval (193 days compared to 316 days). In-app incentives include identification card, rapid laboratory testing results (time-to-results are two business days for 95%), and collection of badges among others. Conclusion: The presented method has changed our donor pool. Besides that, medical staff benefits from the automated process that allows focusing on the donor and their admission. On the other hand, the app has become a valid tool to manage our donor pool and attract first-time and young donors.
Management of Uveitis-Glaucoma-Hyphema Syndrome Caused by Soemmering Ring Cataract: Case Report and Literature Review
Authors: Dubois Charles-David , Yuan Po Hsiang (Shawn) , Durr Georges M.
Published: August 2024

We describe a rare case of Soemmering’s ring-induced uveitis-glaucoma-hyphema (UGH) syndrome, caused by an undisplaced, in-the-bag intraocular lens (IOL) 16 years after implantation. The presenting symptoms were recurrent episodes of transient monocular vision loss, which prompted extensive unremarkable investigations. Ultrasound biomicroscopy (UBM) eventually revealed an enlarging Soemmering’s ring contacting the posterior iris and causing UGH syndrome. This is a unique case because the IOL haptics remained in the bag. Anterior vitrectomy, Soemmering’s ring extraction, IOL exchange to a 3-piece IOL, and implantation of a trabecular meshwork bypass microstent were performed. IOP control and both functional and structural stability were achieved long term. Soemmering’s ring-induced UGH syndrome should be on the differential of a patient with previous cataract surgery and elevated IOP complaining of visual disturbances. Early diagnosis with UBM and surgical intervention may provide optimal outcomes.
Iris Chafing Syndrome Secondary to Iridociliary Adhesions in a Patient with a Single-Piece Acrylic Intraocular Lens: Case Report
Authors: King Jacob , Chen Stephen , Goncz Austin , Palko Joel
Published: August 2024

Introduction: We present a unique case of iris chafing syndrome in a patient with a complex ophthalmologic history after successful placement of a single-piece in-the-bag intraocular lens (IOL) in an eye with healthy zonular support. Case Presentation: A patient with a previous history of multiple retinal surgeries presented with pain and elevated intraocular pressure (IOP) secondary to retained viscoelastic material in the anterior chamber. Following removal of the viscoelastic material in clinic, the patient underwent a combined cataract and glaucoma surgery. Subsequently, the patient developed signs and symptoms of iris chafing syndrome. Anterior segment imaging revealed the cause to be iridociliary adhesion causing an elimination of the sulcus space. Iris chafing syndrome was suspected when the patient presented post-operatively with changes in vision and anterior chamber inflammation. New iris transillumination defects present at the edge of the optic and haptic of the 1-piece lens helped confirm the diagnosis of UGH. Upon further investigation with gonioscopy, ultrasound biomicroscopy and anterior segment optical coherence tomography, it was determined that the patient had iridociliary adhesions. These adhesions eliminated the sulcus space, which resulted in iris chafing. The patient opted for conservative medical management. Best-corrected distance visual acuity remained stable at 20/100 and IOP remained well controlled. Conclusion: A complex ocular history of multiple retinal surgeries and retained viscoelastic material in the anterior chamber resulted in adhesions of the ciliary processes to the iris, leading to UGH syndrome in a patient with an otherwise unremarkable placement of a single-piece in-the-bag IOL.
Long-Term Survival in a Patient with Metastatic Colorectal Cancer Treated with Trifluridine/Tipiracil as Late-Line Chemotherapy: A Case Report
Authors: Karabulut Bülent , Çakar Burcu
Published: August 2024

Introduction: Although long-term survival in patients with metastatic colorectal cancer (mCRC) is limited, treatments for third-line and later treatment are now recommended. We describe a patient who achieved long-term survival when they received third-line treatment with trifluridine/tipiracil (FTD/TPI). Case Presentation: The woman who was 52 years old at diagnosis of adenocarcinoma of the right colon (T3/N0/M1) with metastases to the lung, liver, ovary, and other soft tissues received first-line fluoropyrimidine-based chemotherapy (FOLFOX/FOLFIRI plus bevacizumab) intermittently for approximately 8.5 years with generally stable disease, and second-line FOLFIRI plus radiotherapy. After progression on second-line therapy, the patient initiated treatment with FTD/TPI 35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle. She received a total of 38 cycles of FTD/TPI over a period of 34 months achieving a partial response, maintained performance status, and improved quality of life. Neutropenia was successfully managed with FTD/TPI dose delays or reductions. Conclusion: This heavily pre-treated patient with mCRC demonstrated impressive long-term survival and maintenance of good quality of life with FTD/TPI treatment.
The Impacts of Laparoscopic Restorative Proctocolectomy for Ulcerative Colitis: Systematic Review and Meta-Analysis
Authors: Uchino Motoi , Ikeuchi Hiroki , Horio Yuki , Kuwahara Ryuichi , Kusunoki Kurando , Nagano Kentaro , Kimura Kei , Kataoka Kozo , Beppu Naohito , Ikeda Masataka
Published: August 2024

Introduction: Laparoscopic surgery (LAP) is now recognized as the standard procedure for colorectal surgery. However, the standard surgery for ulcerative colitis (UC) is total proctocolectomy with ileal pouch anal anastomosis (IPAA), which may be an overly complex procedure to complete laparoscopically. We conducted this systematic review and meta-analysis to evaluate the efficacy as well as the advantages and disadvantages of LAP-IPAA in patients with UC stratified by the outcome of interest. Method: We performed a systematic literature review by searching the PubMed/MEDLINE, the Cochrane Library, and the Japan Centra Reuvo Medicina databases from inception until January 2023. Meta-analyses were performed for surgical outcomes, including morbidity and surgical course, to evaluate the efficacy of LAP-IPAA. Results: A total of 707 participants, including 341 LAP and 366 open surgery (OPEN) patients in 9 observational studies and one randomized controlled study, were included. From the results of the meta-analyses, the odds ratio (OR) of total complications in LAP was 1.12 (95% CI: 0.58–2.17, p = 0.74). The OR of mortality for LAP was 0.38 (95% CI: 0.08–1.92, p = 0.24). Although the duration of surgery was extended in LAP (mean difference (MD) 118.74 min (95% CI: 91.67–145.81), p < 0.01) and hospital stay were not shortened, the duration until oral intake after surgery was shortened in LAP (MD −2.10 days (95% CI: −3.52–0.68), p = 0.004). Conclusions: During IPAA for UC, a similar morbidity rate was seen for LAP and OPEN. Although LAP necessitates extended surgery, there may be certain advantages to this procedure, including easy visibility during the surgical procedure or a shortened time to oral intake after surgery.
Closure Grading and Visual Outcome in Patients with Large Idiopathic Macular Holes: A Spectral-Domain Optical Coherence Tomography Observation
Authors: Yu Yanping , Wang Zengyi , Wang Jing , Qi Biying , Liu Lingzi , Jin Zi-Bing , Liu Wu
Published: August 2024

Introduction: So far, there has been no closure grade system synthesizing morphological and microstructural features for large idiopathic macular holes (IMHs) treated by vitrectomy and internal limiting membrane (ILM) peeling. This study aimed to propose a concise one and explore its relevance with visual acuity and the related preoperative factors. Methods: Consecutive patients with large IMHs (minimum diameter >400 μm), undergoing vitrectomy and ILM peeling, obtaining primary closure and regularly followed-up were enrolled. Preoperative clinical charts and spectral-domain optical coherence tomography (SD-OCT) parameters were reviewed. SD-OCT images and best corrected visual acuity (BCVA) were assessed at 1, 4, and 10 months postoperatively. SD-OCT features at last visit were categorized by BCVA significance, and preoperative risk factors were analyzed. Results: Sixty-eight eyes from 64 patients were enrolled. The 10-month postoperative SD-OCT images were categorized into closure grade 1, 2, and 3 with successively decreased BCVA (p < 0.001). During early follow-up, part of grades 2 and 3 could evolve into the upper grade, respectively, but grade 3 could never evolve into grade 1 and exhibited the least satisfactory long-term BCVA. Binary logistic regression showed that large minimum linear diameter (MLD) was a risk factor for grade 3 occurrence (p < 0.001), with a cutoff value of 625.5 μm from the receiver operating characteristic curve for MLD predicting grade 3 occurrence (p = 0.001). Conclusion: Long-term closure status of large IMHs could be categorized into three grades with BCVA significance. Large horizontal MLD is a risk factor for occurrence of grade 3 closure with unsatisfactory visual recovery.
Disseminated Aspergillosis with Mediastinal Invasion Causing Fatal Stroke in an Immunocompetent Young Man
Authors: Yarham Robert , Goh Rudy , Raith Eamon P. , Sundararajan Krishnaswamy , Kleinig Timothy
Published: August 2024

Introduction: Aspergillus flavus is a common cause of aspergillosis. Case Presentation: A previously fit and well, immunocompetent 27-year-old male living in Australia developed disseminated A. flavus complex infection with mediastinal and cardiac invasion, superior vena cava obstruction and stroke, with fatal haemorrhagic transformation. Conclusion: Aspergillus Flavus is a rare but important cause of serious disease in the immunocompetent.
Recurrence of Quadruple Extramammary Paget’s Disease after 12 Years: A Case Report and Literature Review
Authors: Ishiguro Akihiro , Iwashita Nobuhiko , Abe Michihiro , Ogawa Akina , Takeo Tomohiro , Watanabe Daisuke
Published: August 2024

Introduction: Extramammary Paget’s disease (EMPD) is a rare skin cancer that tends to be multicentric, with quadruple EMPD cases being scarcely reported. Case Presentation: We report the case of an 81-year-old man with heterochronous quadruple EMPD. Twelve years after total resection of vulvar EMPD, the patient developed erythematous lesions on the resection margin in the lower abdomen, umbilical region, and both axillae. Histological examination revealed that all lesions were in situ EMPD. Discussion: We reviewed six reported cases of quadruple EMPD with respect to race, sex, site, recurrence, time to recurrence, serum carcinoembryonic antigen, and depth. All patients were elderly Japanese males. In all but one case, the lesions were located in the apocrine region, which is a common site in such as the genital and axillary areas. Our case was the only heterochronous quadruple EMPD. The lesions were limited to the epidermis; therefore, they were unlikely to cause metastasis. It has been reported that the therapeutic effects of imiquimod can be expected in in situ EMPD. Therefore, quadruple EMPD may be a good indication of treatment option. Conclusion: EMPD is a disease whose pathogenesis is not yet clear; however, it is hoped that the origin and aetiology of EMPD will be elucidated from the clinical features of multiple EMPD in the future.
Neurofibromatosis Type 1 Presenting as Bleeding Jejunal Gastrointestinal Stromal Tumour
Authors: Liang Raymond Fueng-Hin , Chau Cora Yuk-Ping , Lim Wee Chian
Published: August 2024

Introduction: Gastrointestinal stromal tumours (GISTs) are an important, though uncommon, cause of obscure gastrointestinal bleeding and may rarely be associated with genodermatoses such as neurofibromatosis type 1 (NF1). NF1-related GISTs have unique phenotypic features compared with sporadic GISTs and may elude diagnosis due to their predilection for the small bowel. Case Presentation: We report a case of a 45-year-old Singaporean woman with café-au-lait macules and cutaneous neurofibromas who presented with occult obscure gastrointestinal bleeding and was eventually discovered to have a bleeding jejunal GIST. This finding, considered together with her cutaneous signs, eventually led to the diagnosis of NF1. Conclusion: Genodermatoses and their gastrointestinal complications are likely under-reported in adult Southeast Asian populations and deserve greater awareness from gastroenterologists practising in this region.
Silicone Granulomas in the Orbit following Breast Implant Rupture: Case Report
Authors: Bohman Elin , Linderoth Rikard , Jonmarker Jaraj Sara , Stålhammar Gustav , Dafgård Kopp Eva
Published: August 2024

Introduction: A known but uncommon complication following breast augmentation with silicone implants is the rupture of these implants and subsequent silicone migration through the lymphatic system. Exceptionally, there are sporadic instances of silicone granulomas forming in distant, non-lymphatic sites, posing diagnostic and management challenges in clinical practice. Case Presentation: A 56-year-old woman presented with slowly progressive diplopia and photosensitivity during the past 12 months. Ophthalmic examination revealed restriction of movement in all gazes in the right eye. Investigation with magnetic resonance imaging and positron emission tomography-computed tomography showed enlarged superior lateral and inferior rectus muscles in the right orbit, and a diffusely enlarged lacrimal gland in the left orbit, as well as a ruptured silicone breast implant on the right side. In addition, multiple enlarged lymph nodes were found throughout the body, as well as a mass in the internal oblique muscle of the abdominal wall. Fine-needle aspiration biopsy of the axillary lymph node and surgical biopsy of extraocular muscles confirmed a diagnosis of silicone granulomas. The patient received anti-inflammatory treatment with intravenous steroids but with no effect on symptoms. Conclusions: This case illustrates a rare instance of silicone dissemination from a ruptured breast implant leading to granuloma formation in multiple organs, including the orbit. Notably, the spread of silicone appeared to occur through both lymphatic and hematogenous routes. This finding underscores the importance of considering silicone granulomas in the differential diagnosis of orbital lesions for patients with a history of silicone implants.
Digital Measures Development: Lessons Learned from an Expert Workshop Addressing Cross-Therapeutic Area Measures of Sleep
Authors: Fromy Piper , Kremliovsky Michael , Mignot Emmanuel , Aloia Mark , Berent Jonathan , Hasan Farah , Hwang Dennis , Poon Jiat-Ling , Malcolm Rebecca , Miller Christopher , Nawa Womba , Bakker Jessie
Published: August 2024

Introduction: The Digital Measures Development: Core Measures of Sleep project, led by the Digital Medicine Society (DiMe), emphasizes the importance of sleep as a cornerstone of health and the need for standardized measurements of sleep and its disturbances outside the laboratory. This initiative recognizes the complex relationship between sleep and overall health, addressing it as both a symptom of underlying conditions and a consequence of therapeutic interventions. It aims to fill a crucial gap in healthcare by promoting the development of accessible, nonintrusive, and cost-effective digital tools for sleep assessment, focusing on factors important to patients, caregivers, and clinicians. Methods: A central feature of this project was an expert workshop conducted on April 19th, 2023. The workshop convened stakeholders from diverse backgrounds, including regulatory, payer, industry, academic, and patient groups, to deliberate on the project’s direction. This gathering focused on discussing the challenges and necessities of measuring sleep across various therapeutic areas, aiming to identify broad areas for initial focus while considering the feasibility of generalizing these measures where applicable. The methodological emphasis was on leveraging expert consensus to guide the project’s approach to digital sleep measurement. Results: The workshop resulted in the identification of seven key themes that will direct the DiMe Core Digital Measures of Sleep project and the broader field of sleep research moving forward. These themes underscore the project’s innovative approach to sleep health, highlighting the complexity of omni-therapeutic sleep measurement and identifying potential areas for targeted research and development. The discussions and outcomes of the workshop serve as a roadmap for enhancing digital sleep measurement tools, ensuring they are relevant, accurate, and capable of addressing the nuanced needs of diverse patient populations. Conclusion: The Digital Medicine Society’s Core Measures of Sleep project represents a pivotal effort to advance sleep health through digital innovation. By focusing on the development of standardized, patient-centric, and clinically relevant digital sleep assessment tools, the project addresses a significant need in healthcare. The expert workshop’s outcomes underscore the importance of collaborative, multi-stakeholder engagement in identifying and overcoming the challenges of sleep measurement. This initiative sets a new precedent for the integration of digital tools into sleep health research and practice, promising to improve outcomes for patients worldwide by enhancing our understanding and measurement of sleep.
Carcinoid Heart Disease and a Complicated Course of Progressive Gastroenteropancreatic Neuroendocrine Neoplasia: A Case Report
Authors: Mohd Nasri Farah Aliyah , Osman Nemer , O'Sullivan Shane
Published: August 2024

Introduction: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a relatively rare, heterogenous group of malignancies originating from secretory cells of the neuroendocrine system. Carcinoid syndrome is a complication of neuroendocrine tumours, characterized by a triad of flushing, bronchospasm, and diarrhoea. This is due to the release of serotonin and other vasoactive substances by the tumour. Elevated levels of serotonin can also cause fibrotic changes in the structures of the heart, which can lead to cardiac complications termed carcinoid heart disease. We report the case of a 64-year-old man diagnosed with carcinoid heart disease 19 years after his initial diagnosis of grade 2 GEP-NET with liver metastases. Case Presentation: The patient presented with symptoms of shortness of breath, lower limb swelling, abdominal swelling, and chest pain. He was on treatment with subcutaneous lanreotide 120 mg twice weekly prior to admission. An echocardiogram showed moderate tricuspid regurgitation and mitral regurgitation but preserved left ventricular systolic function, consistent with right heart failure. A CT pulmonary angiogram showed a small volume left lingula pulmonary embolism with bilateral pleural effusions and stable pericardial effusion with evidence of right ventricular strain. The patient was started on IV furosemide 40 mg twice daily, SC octreotide 100 μg three times daily, and therapeutic tinzaparin. The patient was discharged following successful diuresis. Conclusion: This case report highlights the importance of regular echocardiogram and cardiovascular checkups in patients with carcinoid tumours and liver metastases. A multidisciplinary approach involving medical oncologists, cardiothoracic surgeons, and cardiologists is vital in ensuring early treatment and preventing late-stage complications of carcinoid heart disease.
A Case of Transparent Cornea Maintained after Removal of Dislocated Graft from Descemet’s Stripping Automated Endothelial Keratoplasty
Authors: Nariya Yuta , Ono Takashi , Asahina Yuichi , Kondo Atsushi , Taketani Yukako , Kimakura Mikiko , Toyono Tetsuya , Aihara Makoto , Miyai Takashi
Published: August 2024

Introduction: Corneal graft detachment is a major postoperative complication of Descemet’s stripping automated endothelial keratoplasty (DSAEK). When a corneal graft becomes detached, corneal endothelial function generally fails, and repeat corneal transplantation is required. Herein, we report a rare case in which a transparent cornea was maintained after the removal of a dislocated DSAEK graft. Case Presentation: A 79-year-old woman with a residual lens cortex who had undergone cataract surgery was referred to our hospital. The cortex was removed, and bullous keratopathy progressed. Six months after the initial surgery, DSAEK was performed under topical anesthesia without any complications. Although the corneal graft had attached fairly well, it detached from the host cornea 3 weeks later. Two months after DSAEK, an air tamponade was used to treat the anterior chamber with single interrupted suturing; however, the graft detached again, except for the suture site. Because the detached cornea became cloudy in the anterior chamber, it was surgically removed 8 months after DSAEK. Accordingly, the host cornea transparency improved to a best-corrected visual acuity of 0.8 with a rigid gas permeable lens and a central corneal thickness of 580 μm. The corneal endothelial cell density was 995 cells/mm2. Conclusion: Removal of the corneal graft from the dislocated cloudy graft improved the visual acuity of this patient after DSAEK. The condition of the cornea should be carefully monitored after corneal endothelial transplantation, even after the graft has been dislocated.
Recalcitrant Basal Cell Carcinoma after Grenz Ray Therapy: Introduction of High-Intensity Focused Ultrasound for Minimally Invasive Management
Authors: Serup Jørgen , Zawada Tomasz , Bove Torsten
Published: August 2024

Introduction: Grenz ray therapy popular in dermatology decades ago causes multiple and recalcitrant skin cancer in the treated field many years later. The treatment of choice is surgical excision, but limitations especially disfiguring scarring are a major challenge. We introduce 20 MHz high-intensity focused ultrasound (HIFU) as a new therapy overcoming the limitations of excisional surgery. Case Presentation: A 66-year-old female, who in the 1980s had received several grenz ray treatments of the scalp, developed multiple basal cell carcinomas in the field. She had over 30 excisional surgeries including Mohs surgery in the past with many local complications but, nevertheless, recurrent cancers. HIFU treatments applied to eight basal cell carcinomas and two precancerous lesions resulted in complete clearing at 12-month control, but one recurrence after 15 months. Conclusion: The HIFU treatment is convenient, with very few complications, and applicable to field eradication of skin premalignancies and malignancies. HIFU may fill out a hitherto unmet need of both preventive and curative treatment with better long-term control of patients with recalcitrant skin cancer after grenz ray given in the past. HIFU is a new potentially important therapeutic modality in skin oncology, combining curative treatment, field eradication, and prevention in one procedure through treatment of lesions in different states of progression.
Therapeutic Host Anticancer Immune Response through Photoimmunotherapy for Head and Neck Cancer May Overcome Resistance to Immune Checkpoint Inhibitors
Authors: Koyama Satoshi , Ehara Hiroaki , Donishi Ryohei , Taira Kenkichiro , Fukuhara Takahiro , Fujiwara Kazunori
Published: August 2024

Introduction: Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed hybrid cancer therapy that directly kills cancer cells while producing a therapeutic host anticancer immune response. The activation of host immunity using NIR-PIT can enhance the effects of immune checkpoint inhibitors (ICIs) in animal experimental models; however, there have been no reports of this phenomenon in humans. Furthermore, by activating host immunity using NIR-PIT in patients who have become resistant to ICIs, the effects of ICIs can be restored. Case Presentation: A 56-year-old male experienced local recurrence after chemoradiotherapy for maxillary sinus cancer (cT4bN0M0). The disease had progressed following ICI antiPD-1 antibody therapy. He underwent NIR-PIT for four cycles; however, a local recurrent tumor remained and began a rapid regrowth. The ICI antiPD-1 antibody was then readministered following NIR-PIT. As a result, sensitivity to antiPD-1 therapy was restored, and the tumor shrank. Finally, a complete response was observed without major adverse events associated with subsequent antiPD-1 antibody treatment following NIR-PIT. Conclusion: These results indicated that NIR-PIT may not only activate host anticancer immunity but also enhance the effects of ICIs and overcome antiPD-1 resistance.
Successful EGFR Mutation Detection in Cytological Specimens of Lung Cancer with Challenging Biopsies by Integrating Virtual Bronchoscopy Navigation and Endobronchial Ultrasound Guidance with Highly Sensitive Next-Generation Sequencing: A Case Report
Authors: Umeyama Yasuhiro , Soda Hiroshi , Senju Hiroaki , Ogata Ryosuke , Iwanaga Mizuki , Hayashi Hiroko , Taniguchi Hirokazu , Takemoto Shinnosuke , Takazono Takahiro , Sakamoto Noriho , Fukuda Yuichi , Mukae Hiroshi
Published: August 2024

Introduction: This case report presents the successful detection of an EGFR exon 19 deletion using virtual bronchoscopic navigation (VBN) and endobronchial ultrasound with guide sheath (EBUS-GS) brushing, integrated with highly sensitive next-generation sequencing (NGS), even in challenging biopsy scenarios. The growing prevalence of driver gene alterations in non-small cell lung cancer necessitates effective bronchoscopic technology and reliable multiplex gene NGS panels. However, data regarding the optimal bronchoscopic techniques when using highly sensitive NGS panels are limited. Herein, we report a case utilizing VBN-guided EBUS-GS brushing as an exploratory approach to address this challenge. Case Presentation: A 71-year-old man was evaluated for a band-like lesion near the left pleura during spinal cord infarction. Transbronchial specimens were obtained from lesions invisible on conventional chest radiography and X-ray fluoroscopy using VBN and EBUS-GS brushing. Cytological brushing specimens revealed lung adenocarcinoma, and highly sensitive NGS identified an EGFR exon 19 deletion. He was diagnosed with stage IB disease and underwent radical radiotherapy owing to his fragile condition. If recurrence occurs, the patient will be treated with an EGFR inhibitor. Conclusion: VBN-guided EBUS-GS brushing, a minimally invasive approach, combined with highly sensitive NGS has the potential to provide accurate molecular diagnoses to more patients with lung cancer, thereby offering opportunities for personalized treatment. Our findings warrant further investigation to determine optimal bronchoscopic technologies for obtaining tumor specimens.
Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy
Authors: Barcellini Wilma , Fattizzo Bruno
Published: August 2024

Background: Autoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation. Summary: AIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter. Splenectomy, which is still a good option for young/fit wAIHA, is contraindicated in CAD, and classic immunosuppressants are moving to further lines. Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan). Clinically, AIHAs are highly heterogeneous, from mild/compensated to life-threatening/fulminant, and may be primary or associated with infections, neoplasms, autoimmune diseases, transplants, immunodeficiencies, and drugs. Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging. Key Messages: This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies.
Primary Small Bowel Adenocarcinoma with Metastatic Ovarian Tumor in a Pregnant Woman
Authors: Takahashi Yutaro , Iijima Takayoshi , Ishidera Yumi , Imai Yuichi , Mizushima Taichi , Utsunomiya Daisuke , Kobayashi Noritoshi , Ichikawa Yasushi , Kato Shingo , Harada Jotaro , Miyagi Etsuko
Published: August 2024

Introduction: Primary small bowel carcinoma in pregnant women is extremely rare. Small bowel cancer is difficult to diagnose because of its rarity, lack of specific clinical symptoms, and particular anatomical features. We experienced a case of primary small bowel adenocarcinoma with ovarian metastasis during pregnancy. This is the first reported case of a patient with small bowel adenocarcinoma whose pregnancy continued to term and ended in delivery. Case Presentation: A 32-year-old pregnant woman developed abdominal pain, and imaging examination revealed an ovarian tumor at 29 weeks of gestation. We performed laparotomy and resected the ovarian tumor, which was initially suspected to be primary ovarian cancer. The patient continued the pregnancy to term. A detailed examination of the abdominal cavity during cesarean delivery at 37 weeks revealed that the primary lesion was located in the small bowel. Conclusion: It is important to recognize that the small bowel may be the primary site of metastatic ovarian cancer. Detailed and careful examination is necessary to diagnose small bowel cancer during pregnancy.