Published Case Reports Research Articles

P277 The epidemiology, clinical manifestations and outcomes of cerebral mucormycosis: A systematic review

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesMucormycosis is a devastating infection caused by Mucorales order ubiquitously existing in the environment. Cerebral mucormycosis, the mortal manifested type of brain infection, is commonly seen in association with deep immunocompromised status. Despite lethality of brain mucormycosis, the lack of consensus data specifically concerning clinical manifestations, radiographical characteristics, diagnosis methods, and management are severely felt.MethodsIn this systematic review and meta-analysis, we searched PubMed and Scopus (up to December 31, 2018) using the combination of the following keywords: (‘Mucor*’ or ‘Zygomyc*’) and (‘cereb*’ or ‘brain’ or ‘central nervous system’ or ‘intracranial’) and found ∼1462 articles.Only published case reports or case series with the definition of cerebral mucormycosis (finding the signs of this invasive mold in histopathological section or mycological examination and the presence of histopathological or radiological signs of brain involvement) were included. However, animal mucormycosis and papers in languages other than English or duplicates were excluded. Overall, 287/1462 articles were reviewed and included consisting of 345 cases of cerebral mucormycosis.ResultsA total of 206 (59.7%) patients were male. The most common risk factor was diabetes mellitus (51%), followed by hematological malignancies (23.8%). Remarkably, among hematological malignancies, acute lymphoblastic leukemia was significantly associated with cerebral mucormycosis (P <.001). In terms of reported risk factors, only 16.3% of patients had hematological malignancies till 2000, while the percentage of cases (29.7%) with this risk factor increased significantly after 2000 (P = .04). The most common clinical symptoms were orbital (46.4%) and neurological symptoms (41.2%), while headache was present in 35.9% of patients and fever only in 0.6%. Of the patients reported, 60.6% died and there was a significant correlation between mortality rate and diabetes mellitus (P = .003), while the mortality rate was not associated with other risk factors such as hematological malignancies.Conclusions: In patients with mucormycosis, the presence of orbital clinical symptoms may suggest cerebral involvement as much as the presence of neurologic symptoms. Finally, it can be said that Cerebral Mucormycosis is a very fatal mold infection, especially if it occurs in diabetic patients.

P196 A rare presentation of subcutaneous Entomophthoramycosis

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMEntomophthoramycosis is a chronic granulomatous type of subcutaneous infection seen mainly in immunocompetent individuals. The usual focus of Conidiobolomycosis infection is as rhinoentomophthoramycosis, characterized by chronic, indolent, and localized swelling of the nose, paranasal tissues, sinuses, cheeks, and upper lips and it infrequently affects the lower extremities. We report a case of subcutaneous Conidiobolomycosis in a 21-year-old male with an alleged history of trauma to left foot by a wooden stake 6 months back. Primary treatment of the wound was done at a local hospital. A total of 4 months post-trauma he developed multiple pus discharging sinuses on the dorsal and plantar aspects of the left foot, for which local dressing was done in a nearby hospital. He presented to our hospital with non-healing multiple sinuses, with active serosanguinous discharge. He underwent wound debridement under spinal anesthesia and tissue was sent for fungal culture, histopathological examination. Aerobic culture of the wound swab revealed moderate growth of Methicillin-resistant Staphylococcus aureus sensitive to clindamycin, gentamicin, and linezolid. Histopathological examination of the tissue showed a resolving abscess with granulation tissue. Direct microscopic examination of the tissue by KOH mount showed no fungal elements. It was inoculated into Sabouraud's dextrose agar with and without cycloheximide and incubated at both 25°C and 37°C. Sabouraud's dextrose agar without cycloheximide incubated at 37°C after 48 h of incubation grew cream-colored glabrous colonies adherent to surface with pale reverse. Lactophenol cotton blue preparation revealed broad, sparsely septate hyphae with primary conidia which are globose approx. 40 μm is diameter, produced singly. They have a characteristic protruding papilla on one side. The fungal isolate was identified as Conidiobolus species. Sequencing results are awaited for species identification and confirmation. Serial wound dressings were done following strict infection control policies and he was started on tablet linezolid 600 mg twice daily, tablet itraconazole 400 mg twice daily for 1 week, followed by 400 mg once daily for 6 months. Conidiobolus is a soil saprophyte, found in decaying vegetation in most warm climates in tropical countries. There has been only one published case report of subcutaneous entamophthoramycosis of the foot, in a 49-year-old female from Venezuela. To the best of our knowledge, we report the first case of subcutaneous entamopthoramycosis of the lower extremity in India and the second case in the world.

A case of novel DYT6 dystonia variant with serious complications after deep brain stimulation therapy: a case report

BackgroundDYT6 dystonia belongs to a group of isolated, genetically determined, generalized dystonia associated with mutations in the THAP1 gene.Case presentationWe present the case of a young patient with DYT6 dystonia associated with a newly discovered c14G>A (p.Cys5Tyr) mutation in the THAP1 gene. We describe the clinical phenotype of this new mutation, effect of pallidal deep brain stimulation (DBS), which was accompanied by two rare postimplantation complications: an early intracerebral hemorrhage and delayed epileptic seizures. Among the published case reports of patients with DYT6 dystonia, the mentioned complications have not been described so far.ConclusionsDBS in the case of DYT6 dystonia is a challenge to thoroughly consider possible therapeutic benefits and potential risks associated with surgery. Genetic heterogeneity of the disease may also play an important role in predicting the development of the clinical phenotype as well as the effect of treatment including DBS. Therefore, it is beneficial to analyze the genetic and clinical relationships of DYT6 dystonia.

Vanishing bile duct syndrome after drug-induced liver injury

BackgroundVanishing bile duct syndrome (VBDS) is a serious cholestatic liver disease that can be a complication of drug-induced liver injury (DILI). While journals have published case reports of this condition, large studies on a cohort of these patients are lacking. We aimed to compile published case reports and case series of patients with VBDS and DILI to describe the clinical and laboratory characteristics of the disease and identify factors associated with good and poor outcomes. MethodsWe included case reports and case series of VBDS secondary only to DILI. We extracted demographic, clinical, laboratory, treatment, and exposure data from each case report and categorized cases by outcome, good versus poor. We defined poor outcomes as cases with severe long-term complications or death. We analyzed risk factors for poor outcomes using logistic regression. ResultsWe identified a total of 59 eligible cases. Of those, 39 (59%) were female, the median age was 36 (IQR:12–58), and 18 (31%) were pediatric cases (≤18 years). The most common offending drug class was antibiotics, especially beta-lactams. Patients with increased total bilirubin (OR=4.69; 95% CI=1.55–15.49; p = 0.008), increased direct bilirubin (OR=6.50; 95% CI=1.34–48.91; p = 0.034), lower liver synthetic activity (OR=0.11; 95% CI=0.02–0.55; p = 0.013), and older age (OR=3.31; 95% CI=1.15–10.04; p = 0.029) were more likely to develop poor outcomes. ConclusionsIn patients with VBDS and DILI, antibiotics were the most common offending agents. Higher total and direct bilirubin levels were associated with poor outcomes.

Publication ethics: Patient consent for publishing case reports of adverse drug reactions is important yet absent from several recent manuscripts

Case reports of adverse drug reactions (ADRs) constitute an important source of medication safety information. Detailed description of patients in such reports could potentially make subjects identifiable, thereby emphasizing the importance of consent for publication. The Committee on Publication Ethics and the International Committee of Medical Journal Editors recommend obtaining patient consent prior to publishing potentially identifiable patient information. However, this report shows absence of information regarding patient consent for publication from several recently-published ADR case reports. A sample of 100 most-recent ADR case reports with free full-text indexed in PubMed was qualitatively reviewed for information regarding publication consent and other ethical disclosures. Of the 100 most-recently-published ADR case reports, only 52 (52%) manuscripts clearly described obtaining patient consent for publication. Thirty-seven (37%) manuscripts made no mention of such consent or approval from an ethics committee. Eleven (11%) manuscripts contained ethical disclosures such as patient consent to undergo treatment and study approval from an institutional ethics committee, but without a clear statement regarding patient consent for publication. A significant number of recently-published ADR case reports do not clearly describe if patient consent for publication was obtained. This could be attributable to various factors, including lack of clarity in journals’ guidelines regarding publication consent for case reports and dilemma regarding what constitutes identifiable patient information. This report calls for diligence of all stakeholders involved in medical manuscript publishing, viz. authors, manuscript reviewers, editors, and journal publishers to ensure that information regarding patient consent for publication is properly disclosed in ADR case reports.

1581P Neuromuscular and cardiac adverse events associated with immune checkpoint inhibitors (ICIs): Pooled analysis of individual cases from multiple institutions and literature

Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple tumors, due to improved efficacy, quality of life and safety. While most immune-related adverse events (irAEs) are mild and easily managed, in rare cases such events may be life-threatening, especially those affecting the neuromuscular and cardiac system. The management of neuromuscular/cardiac irAEs is not clear due to the lack of consistent data. Therefore, we performed a pooled analysis of collected cases from selected Italian centers and individual data from published case reports and case series, in order to improve our understanding of these irAEs. We collected retrospective data from patients treated in 6 Italian centers with ICIs (PD-1 or PD-L1 and/or CTLA-4 inhibitor) for any solid tumor who experienced neuromuscular and/or cardiovascular toxicity. Then, to increase the caseload, we performed a search of case reports and series of neuromuscular/cardiac irAEs from ICIs with any solid tumor. Our analysis includes cases from our institutions (n=18) and the case reports identified in our systematic literature search (n=112), for a total of 130 patients. Among these patients, 44 had complete resolution of their neuromuscular/cardiac irAEs, in 21 there was a clinical improvement with mild sequelae, and 52 patients died as a result of the irAEs. Factors significantly associated with worse outcomes were the earlier irAE onset, within the first 2 cycles of ICI (Fisher P< 0.0001), clinical manifestation of both myositis and myocarditis if compared to patients who developed only myositis or myocarditis (Chi-square P= 0.0051), increased peak troponin value ((Mann-Whitney P= 0.0346) and the development of arrythmia (Fisher P= 0.0051). To our knowledge, this is the widest collection of individual cases of immune-related myocarditis/myositis. Early irAE onset, concurrent development of myositis and myocarditis, increased peak troponin value and occurrence of arrythmias are associated with worse outcomes and should encourage an aggressive immunomodulatory treatment.

Research Trends and Impact Factor on PubMed Among General Medicine Physicians in Japan: A Cross-Sectional Bibliometric Analysis.

BackgroundJapan created a specialty system for general medicine in 2018. However, Japanese academic generalists’ contribution to research remains unclear. This study examines the popularity of Japanese general medicine research, the characteristics of journal publications, annual trends, and the characteristics/differences among publications in journals with an impact factor (IF).MethodsThis bibliometric analysis extracted international, English-language, journal articles published on PubMed between January 1, 2015, and December 31, 2020. Analysis included articles with either the first, second, or last author in general medicine. We classified articles according to publication or article type and field of research. We obtained standard descriptive statistics for each publication type. Chi-squared test or Fisher’s exact test was used to compare nominal variables. For continuous variables, t-tests or Wilcoxon rank-sum tests were used, as appropriate.ResultsOf the 2372 articles analyzed, original articles were most common (56.3%), followed by case reports (30.1%), reviews (7.63%), and letters/others (5.9%). Publication volume increased 2.64-fold annually over 5 years. Clinical research (60.5%) was most common among original articles, followed by basic experimental research (17.5%) and public health/epidemiology (12.7%). Medical quality and safety (4.1%), medical and clinical education (3.1%), and health services (1.42%) received comparatively little attention. Eighty percent of articles were published in journals with IF; however, these journals rarely published case reports. Among original articles, the likelihood of publishing in journals with IF was high for basic laboratory medicine articles with higher IF (median IF 3.83, OR 1.71, 95% CI 2.20–5.95, p=0.044) and lower for clinical education research with the lowest IF (median IF 1.83, OR 0.56, 95% CI 01.8–0.75, p<0.001).DiscussionGeneral medicine physicians’ international research output is increasing in Japan; however, research achievements have not been generalized, but rather much influenced by clinical subspecialty backgrounds. This will likely continue unless an academic generalist discipline is established.

Rectosigmoid screwdriver perforation presenting as a strangulated inguinal hernia

We present a case of a young male patient with no previously known medical, surgical or psychiatric history, who was referred to our institution as an irreducible left inguinal hernia with signs of strangulation. Intraoperative findings, however, revealed a retained foreign body at the rectosigmoid junction, which had previously perforated through the floor of the inguinal canal, essentially sealing off the contamination into the inguinal canal and contributing to the clinical presentation of a left inguinal hernia. This is, to our knowledge, the first published case report locally and internationally concerning rectosigmoid-inguinal canal perforation with the working end of a screwdriver.

Desmoplastic Fibroblastoma of the Supraclavicular Region: A Rare Soft-Tissue Tumor With a Review from the Last Decade.

Desmoplastic fibroblastoma (DF) is primarily a sporadic, rare, benign, soft-tissue tumor with an excellent prognosis and no reported recurrence to date. DF presents as a painless, slow-growing mass with symptoms due to its mass effect. We report a case of a middle-aged man presenting with a right supraclavicular mass and numbness of the right arm, eventually diagnosed as DF. After confirming the diagnosis with imaging and biopsy studies, the tumor was successfully excised using a transcervical approach with no complication or recurrence detected during the 2-year follow-up after surgery. A review of the relevant literature is presented regarding the presentation, diagnosis, and outcomes of published case reports of DF coinciding with those of our discussed case. This case report adds to the pool of uncommon DF cases mainly for its unique symptoms and location. It also highlights the necessity of health education related to painless masses that might be attributed as trivial in the community.

Modulating effects of FGF12 variants on NaV1.2 and NaV1.6 being associated with developmental and epileptic encephalopathy and Autism spectrum disorder: A case series.

SummaryObjectiveFibroblast Growth Factor 12 (FGF12) may represent an important modulator of neuronal network activity and has been associated with developmental and epileptic encephalopathy (DEE). We sought to identify the underlying pathomechanism of FGF12-related disorders.MethodsPatients with pathogenic variants in FGF12 were identified through published case reports, GeneMatcher and whole exome sequencing of own case collections. The functional consequences of two missense and two copy number variants (CNVs) were studied by co-expression of wildtype and mutant FGF12 in neuronal-like cells (ND7/23) with the sodium channels NaV1.2 or NaV1.6, including their beta-1 and beta-2 sodium channel subunits (SCN1B and SCN2B).ResultsFour variants in FGF12 were identified for functional analysis: one novel FGF12 variant in a patient with autism spectrum disorder and three variants from previously published patients affected by DEE. We demonstrate the differential regulating effects of wildtype and mutant FGF12 on NaV1.2 and NaV1.6 channels. Here, FGF12 variants lead to a complex kinetic influence on NaV1.2 and NaV1.6, including loss- as well as gain-of function changes in fast and slow inactivation.InterpretationWe could demonstrate the detailed regulating effect of FGF12 on NaV1.2 and NaV1.6 and confirmed the complex effect of FGF12 on neuronal network activity. Our findings expand the phenotypic spectrum related to FGF12 variants and elucidate the underlying pathomechanism. Specific variants in FGF12-associated disorders may be amenable to precision treatment with sodium channel blockers.FundingDFG, BMBF, Hartwell Foundation, National Institute for Neurological Disorders and Stroke, IDDRC, ENGIN, NIH, ITMAT, ILAE, RES and GRIN

Allergic Fungal Rhinosinusitis: The Role and Expectations of Biologics

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS.

OARD: Open annotations for rare diseases and their phenotypes based on real-world data

Diagnosis for rare genetic diseases often relies on phenotype-driven methods, which hinge on the accuracy and completeness of the rare disease phenotypes in the underlying annotation knowledgebase. Existing knowledgebases are often manually curated with additional annotations found in published case reports. Despite their potential, real-world data such as electronic health records (EHRs) have not been fully exploited to derive rare disease annotations. Here, we present open annotation for rare diseases (OARD), a real-world-data-derived resource with annotation for rare-disease-related phenotypes. This resource is derived from the EHRs of two academic health institutions containing more than 10 million individuals spanning wide age ranges and different disease subgroups. By leveraging ontology mapping and advanced natural-language-processing (NLP) methods, OARD automatically and efficiently extracts concepts for both rare diseases and their phenotypic traits from billing codes and lab tests as well as over 100 million clinical narratives. The rare disease prevalence derived by OARD is highly correlated with those annotated in the original rare disease knowledgebase. By performing association analysis, we identified more than 1 million novel disease-phenotype association pairs that were previously missed by human annotation, and >60% were confirmed true associations via manual review of a list of sampled pairs. Compared to the manual curated annotation, OARD is 100% data driven and its pipeline can be shared across different institutions. By supporting privacy-preserving sharing of aggregated summary statistics, such as term frequencies and disease-phenotype associations, it fills an important gap to facilitate data-driven research in the rare disease community.

Network Effects of Brain Lesions Causing Central Poststroke Pain.

This study was undertaken to test whether lesions causing central poststroke pain (CPSP) are associated with a specific connectivity profile, whether these connections are associated with metabolic changes, and whether this network aligns with neuromodulation targets for pain. Two independent lesion datasets were utilized: (1) subcortical lesions from published case reports and (2) thalamic lesions with metabolic imaging using 18F- fluorodeoxyglucose positron emission tomography-computed tomography. Functional connectivity between each lesion location and the rest of the brain was assessed using a normative connectome (n=1,000), and connections specific to CPSP were identified. Metabolic changes specific to CPSP were also identified and related to differences in lesion connectivity. Therapeutic relevance of the network was explored by testing for alignment with existing brain stimulation data and by prospectively targeting the network with repetitive transcranial magnetic stimulation (rTMS) in 7 patients with CPSP. Lesion locations causing CPSP showed a specific pattern of brain connectivity that was consistent across two independent lesion datasets (spatial r= 0.82, p< 0.0001). Connectivity differences were correlated with postlesion metabolism (r= -0.48, p< 0.001). The topography of this lesion-based pain network aligned with variability in pain improvement across 12 prior neuromodulation targets and across 32 patients who received rTMS to primary motor cortex (p< 0.05). Prospectively targeting this network with rTMS improved CPSP in 6 of 7 patients. Lesions causing pain are connected to a specific brain network that shows metabolic abnormalities and promise as a neuromodulation target. ANN NEUROL 2022;92:834-845.

The road from discovery to healing: What does it take?

Education and career choices are two major life decisions.1 One who considers a degree in Medicine may ask: “am I up to the challenge,” “am I curious about how medicine improves life,” and “do I care profusely about human life?” Practicing clinical medicine is the most common path; but, not all those with a career in Medicine are physicians. There are researchers in the basic sciences, and there are inventors and innovators of biomedical devices. All those working in Medicine start with valuing and pursuing the improvement of life.&#x0D; The ideal medical school integrates disciplines for a complete understanding of medicine.2 Two of the articles in this edition describe challenges facing Philippine medical schools. The first article re-evaluates the adjustment factor used in the admission process. The second article highlights flexibility and innovation in the sudden shift to online learning.&#x0D; The MD-PhD Program connects scientific research with clinical practice. In the US, this program started in the 1950s and expanded through the Medical Scientist Training Program to more than 90 active MD-PhD programs in 2016.3 The country’s first MD-PhD Program started in 2010 at the University of the Philippines College of Medicine (UPCM). One of our physician-scientist graduates authored an article on the pharmacologic potential of locally harvested edible mushrooms.&#x0D; Many other UPCM graduates do research at the Philippine General Hospital. As an academic medical center, it houses “a large and diverse sample of patients, experienced and interested investigators, with organizational support.”4 In this edition, physician trainees and faculty authored or mentored seven studies. They study various disease and systems processes with the goal of health promotion.&#x0D; Three articles studied hospital processes related to health service delivery. Radiation oncologists explored delays in repeated CT simulation for the radiation of head and neck cancer patients. Ophthalmologists formed a time quality management team to reduce the total consultation time at their outpatient clinic. OB-GYN sonologists looked at methods of manual disinfection of transvaginal probes to keep patients safe while undergoing such procedures.&#x0D; Two articles studied the epidemiology of cerebrovascular diseases and neoplasms (periampullary malignancies), two of the top causes of mortality in the country. Two other studies looked at diseases that affect the quality of life: visual impairment in the young, and the use of a modified approach to hip arthroplasty.&#x0D; Case reports remain valuable sources of unusual information and new ideas.5 This edition also features a case report on a rare childhood malignancy found in an elderly patient who was successfully treated.&#x0D; The road from discovery to healing can take many forms as exemplified by the 11 articles in this edition of Acta Medica Philippina. Publication is a step on the road from discovery to healing. To complete the journey is to implement their findings in clinical practice. Many implementation challenges exist due to differing approaches.6&#x0D; The road from discovery to healing is not an easy one. We hope to close the gap between evidence and practice; we contribute to an ever-evolving and growing body of knowledge; and we offer the best treatment to our patients, the lives we value the most.&#x0D; &#x0D; Jean Anne B. Toral, MD, MSc Department of Obstetrics and Gynecology College of Medicine and Philippine General Hospital University of the Philippines Manila Coordinator for Research and Chief of the Expanded Hospital Research Office, Philippine General Hospital&#x0D; &#x0D; REFERENCES &#x0D; &#x0D; Camilleri AR. What are life’s biggest decisions? [Internet]. 2021 [cited June 2022]. Available from: https://www.psychologytoday.com/us/ blog/life-s-biggest-decisions/202101/what-are-lifes-biggest-decisions&#x0D; Napier S. Rapid response: the characteristics of an ideal medical school. BMJ. 2019; 323:1437.&#x0D; Harding CV, Kahn JR, Akabas MH, Andersen OS. History and outcomes of fifty years of physician-scientists training in medical scientist training programs. Acad Med. 2017 Oct; 92(10):1390-8.&#x0D; Pinsky WW. The roles of research in an academic medical center. The Ochsner Journal. 2000 Oct; 2(4):201-2.&#x0D; Loubon CO, Culquichicon C, Correa R. The importance of writing and publishing case reports during medical training. Cureus. 2017 Dec;9(12):e1964.&#x0D; Kristensen N, Nymann C, Konradsen H. Implementing research results in clinical practice – the experiences of healthcare professionals. BMC Health Sciences Research. 2016; 16:48.&#x0D;

Metformin toxicity: A meta-summary of case reports.

BACKGROUNDMetformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes. Due to the lack of randomized control trials, most of the data pertaining to the clinical course, therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series. AIMTo analyse the symptomology, clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODSWe performed a systematic search from PubMed, Science Direct, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and Google Scholar databases using the terms “metformin” AND “toxicity” OR “overdose” OR “lactic acidosis” OR “hyperlactatemia”. The inclusion criteria were: (1) Case reports or case series with individual patient details; and (2) Reported toxicity or overdose of metformin in adults, published in the English language. Data regarding baseline demographics, clinical presentation, therapeutic interventions, intensive care unit course and overall outcome were collected. RESULTSTwo hundred forty-two individual cases were analysed, from 158 case reports and 26 case series, with a cumulative mortality of 19.8%. 214 (88.4%) patients were diabetics on metformin. 57 (23.6%) had acute ingestion, but a great majority (76.4%) were on metformin in therapeutic doses when they developed toxicity. Metformin associated lactic acidosis (MALA) was the most commonly reported adverse effect present in 224 (92.6%) patients. Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia. The organ support used was renal replacement therapy (RRT) (68.6%), vaso-pressors (58.7%) and invasive mechanical ventilation (52.9%). A majority of patients (68.6%) received RRT for toxin removal, renal dysfunction and correction of MALA. Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.CONCLUSIONMost of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions. These patients may develop severe lactic acidosis, leading to significant morbidity and need for organ support. Despite severe MALA and the need for multiple organ support, they may have good outcomes, especially when RRT is used. The dose of metformin, serum pH, lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.

Acute-Onset Visual Snow Syndrome After LASIK

PURPOSE: To describe a case of acute-onset visual snow syndrome occurring after bilateral myopic laser in situ keratomileusis (LASIK). METHODS: Case report. RESULTS: A 38-year-old man presented with a 7-month history of constant positive visual disturbances involving his entire binocular visual field after bilateral LASIK. The patient described his symptoms as a “moving texture” present at all times in all lighting conditions that he noticed beginning the evening of the same day he had LASIK. The phenomenon was worse in low lighting and was in fact present in complete darkness, even when his eyes were closed. The patient also endorsed large halos, nyctalopia, and enhanced entoptic phenomena in both eyes, all of which had subjectively worsened after LASIK. Topography-guided customized ablation treatment enhancement had been performed to reduce the patient's symptoms without success. On presentation, uncorrected distance visual acuity was 20/16 in both eyes. Results of slit-lamp examination and corneal imaging were unremarkable in both eyes. The patient was eventually fit with scleral contact lenses, which reduced his halos at night but did not improve his visual snow symptoms. CONCLUSIONS: Although visual snow and visual snow syndrome have been known to present suddenly in a subset of cases, this is the first published case report of acute-onset visual snow syndrome immediately after refractive surgery. Visual snow syndrome has reportedly been preceded by specific events, including migraine attacks, medications, and trauma. Because the symptoms are non-ocular in origin, further refractive surgery enhancement is not indicated. [ Journal of Refractive Surgery Case Reports. 2022;2(3):e51–e54.]

Topiramate-induced acute angle-closure glaucoma: A case report and review of literature

Drug-induced angle-closure glaucoma is an emergency associated with potentially vision threatening side effects. There are various classes of drugs which induce acute angle-closure glaucoma. Topiramate is an oral sulfa-based drug used for seizure, migraine, and neuropathic pain. There are published case reports of topiramate-induced angle-closure which can mimic acute angle-closure glaucoma. We present a case of a 32-year-old female who developed bilateral angle-closure glaucoma secondary to topiramate.

253 Clinical characteristics and treatment outcomes of sweet syndrome

Background: Sweet syndrome (SS) is a rare inflammatory skin condition. Current available data is limited to case reports or small case series. Objective: To describe the clinical characteristics and treatment outcomes of published cases of SS. Methods: Search was conducted in OVID Medline in 2021 for all published case reports and case series. A total of 509 articles were included. Results: The 537 cases comprised of 55.4% (296) females & 44.6%(238) males, with a mean age of 49 years. Of all, 43.6 %(234) cases were classic/idiopathic SS; 28.9 %(155) cases had malignancy associated SS; and 27.6 %(148) cases of drug-induced SS.

Pericardial malignant infiltration as the cause of sudden death of a patient with metastatic urothelial carcinoma treated with atezolizumab

BackgroundMuscle-infiltrating urothelial carcinoma of the bladder is the most common genitourinary cancer. Immunotherapeutic agents targeting protein-1 programmed death or protein-1 programmed death ligand are currently considered the standard treatment in patients with either inoperable locally advanced or metastatic urothelial carcinoma (MUC) after platinum-based chemotherapy failure.Case presentationHere we report the case of a Caucasian male patient with metastatic urothelial carcinoma treated with second-line atezolizumab within a trial who achieved complete response by computed tomography (CT), but suddenly died due to cardiac tamponade resulting from malignant pericardial infiltration. Histopathology confirmed this as the only site of disease progression.ConclusionsCardiovascular toxicity of atezolizumab was considered within differential diagnoses, however histopathological examination revealed progression of malignancy in the pericardium as the cause of the sudden death. This is the first published case report of a patient treated with second-line atezolizumab in whom the rare disease progression of pericardial infiltration was confirmed. Despite its rarity, the clinicians should always consider the possibility of pericardial metastases.

Evaluating the rare cases of cortical vertigo using disconnectome mapping

In rare cases, cortical infarcts lead to vertigo. We evaluated structural and functional disconnection in patients with acute vertigo due to unilateral ischemic cortical infarcts compared to infarcts without vertigo in a similar location with a focus on the connectivity of the vestibular cortex, i.e., the parieto-opercular (retro-)insular cortex (PIVC). Using lesion maps from the ten published case reports, we computed lesion–functional connectivity networks in a set of healthy individuals from the human connectome project. The probability of lesion disconnection was evaluated by white matter disconnectome mapping. In all ten cases with rotational vertigo, disconnections of interhemispheric connections via the corpus callosum were present but were spared in lesions of the PIVC without vertigo. Further, the arcuate fascicle was affected in 90% of the lesions that led to vertigo and spared in lesions that did not lead to vertigo. The lesion–functional connectivity network included vestibulo-cerebellar hubs, the vestibular nuclei, the PIVC, the retro-insular and posterior insular cortex, the multisensory vestibular ventral intraparietal area, motion-sensitive areas (temporal area MT+ and cingulate visual sulcus) as well as hubs for ocular motor control (lateral intraparietal area, cingulate and frontal eye fields). However, this was not sufficient to differentiate between lesions with and without vertigo. Disruption of interhemispheric connections of both PIVC via the corpus callosum and intra-hemispheric disconnection via the arcuate fascicle might be the distinguishing factor between vestibular cortical network lesions that manifest with vertigo compared to those without vertigo.