Sarcopenia and aortic valve disease.

Valvular heart disease, including calcific or degenerative aortic stenosis (AS), is increasingly prevalent among the older adult population. Over the last few decades, treatment of severe AS has been revolutionised following the development of transcatheter aortic valve replacement (TAVR). Despite improvements in outcomes, older adults with competing comorbidities and geriatric syndromes have suboptimal quality of life outcomes, highlighting the cumulative vulnerability that persists despite valve replacement. Sarcopenia, characterised by loss of muscle strength, mass and function, affects 21%-70% of older adults with AS. Sarcopenia is an independent predictor of short-term and long-term outcomes after TAVR and should be incorporated as a prognostic marker in preprocedural planning. Early diagnosis and treatment of sarcopenia may reduce morbidity and mortality and improve quality of life following TAVR. The adverse effects of sarcopenia can be mitigated through resistance training and optimisation of nutritional status. This is most efficacious when administered before sarcopenia has progressed to advanced stages. Management should be individualised based on the patient's wishes/preferences, care goals and physical capability. Exercise during the preoperative waiting period may be safe and effective in most patients with severe AS. However, future studies are needed to establish the benefits of prehabilitation in improving quality of life outcomes after TAVR procedures.

HIV-associated disseminated cryptococcosis-An unusual clinical and diagnostic picture with successful cure by single dose liposomal amphotericin B treatment.

BACKGROUND: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection. METHODS AND RESULTS: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine. CONCLUSION: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals.

Roussy-Lévy Syndrome: Pes Cavus, Tendon Areflexia, Amyotrophy, Gait Ataxia, and Upper Limb Tremor in a Patient with CMT Neuropathy.

Background: Roussy-Lévy syndrome (RLS) is characterized by postural hand tremor seen in patients with familial autosomal dominant Charcot-Marie-Tooth (CMT) neuropathy. Phenomenology Shown: This video demonstrates irregular, jerky bilateral kinetic, postural, rest tremor affecting the right > left hand, along with pes cavus and gait ataxia in a patient with CMT disease. Educational Value: Pes cavus, tendon areflexia, sensory ataxia, and upper limb tremor should prompt consideration of CMT neuropathy. Highlights: This video abstract depicts a bilateral hand tremor characteristic of Roussy-Lévy syndrome seen in patients with Charcot-Marie-Tooth disease neuropathy. The significance of the abstract lies in the phenomenology and the physiology of the tremor seen in patients with genetically confirmed duplication of PMP22 gene.

Pneumocystis jirovecii pneumonia: a case report.

INTRODUCTION AND IMPORTANCE: Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus (HIV) + patients. We describe a case of PJP pneumonia which provided a diagnostic challenge in a patient who presented with no known risk factors leading to a delay in initiation of appropriate antibiotic therapy. CASE PRESENTATION: A 71-year-old previously healthy white/Caucasian male presented with subacute hypoxic respiratory failure due to multifocal pneumonia with diffuse bilateral ground glass opacities with consolidations despite prior treatment with antibiotics and steroids. He was admitted and started on intravenous broad-spectrum antibiotics but continued to deteriorate, eventually requiring intubation and transfer to the ICU. Bronchoscopy revealed PJP and treatment was initiated, but the patient developed refractory shock and multiorgan failure, and ultimately died. It was later discovered that he was HIV-1 positive. CLINICAL DISCUSSION: PJP, as a potential cause of his presentation, was not considered given that our patient lacked any overt risk factors for PJP pneumonia. He continued to worsen despite broad spectrum antibiotic therapy and hence bronchoscopy was pursued. His clinical profile, in hindsight, was suspicious for PJP pneumonia and early PJP-directed antibiotic therapy may have prevented a fatal outcome, as in this case. There was an element of cognitive bias across multiple providers which may have contributed to the delay in treatment despite his rapid clinical decline while on conventional pneumonia treatment protocol. His diagnosis was later evident when his BAL-DFA grew PJP in addition to his low levels of CD4 and CD8 cells. He was found to be HIV-1 positive five days after his death; there was a delay in this diagnosis since all positive HIV tests from the hospital are reported as 'pending' until the presumptive positive sample goes to the Connecticut Department of Public Health State laboratory for the confirmatory test. PJP-targeted therapies were initiated later in our patient's hospital course when the infection had progressed to refractory septic shock with multiorgan failure and eventual death. CONCLUSION: PJP pneumonia is a fatal disease if not recognized early in the course of illness, and the patient usually undergoes multiple antibiotic regimens before they are diagnosed and receive appropriate clinical care. The gold standard of diagnostic testing for PJP is by obtaining bronchial washings through a flexible bronchoscopy and the turnaround time for such results may take a few days to result. A significant proportion of patients may not have any overt risk factors of immunosuppression and early empiric treatment for PJP may be clinically appropriate as the delay in diagnosis may be associated with significant morbidity and mortality risk.

Resistance Training in Patients After Metabolic and Bariatric Surgery: Protocol for a Systematic Review.

BACKGROUND: Resistance training has been consistently shown to have multiple health benefits, especially for patients who have undergone bariatric surgery. Patients who have undergone bariatric surgery are recommended to participate in resistance exercise; however, protocols and guidelines for resistance training remain poorly implemented. OBJECTIVE: This is a protocol for a systematic review and possibly a meta-analysis that will synthesize evidence of the effects of resistance exercise on changes in body composition, muscular strength, overall weight loss or maintenance of weight loss, and quality of life in patients after metabolic and bariatric surgery (MBS). The findings of this study may provide practice recommendations for resistance training among patients who have undergone MBS. METHODS: We registered this systematic review on PROSPERO (CRD42023464928) on September 18, 2023. A systematic search of electronic databases (Embase, PubMed, Scopus, Web of Science, and CINAHL) was conducted on studies published from January 1, 1991, to May 15, 2023, to identify English-language human studies on adult patients who have undergone MBS that include a resistance training intervention and describe outcome measurements of body composition or strength. Screening will be performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and relevant data elements will be extracted. RESULTS: Searches and screenings commenced in May 2023. Data extraction and analyses will be completed by the end of December 2023, after which findings will be synthesized and reported by the end of March 2024. CONCLUSIONS: This systematic review will summarize the evidence regarding resistance training in patients after MBS. The findings from this systematic review and possible meta-analysis may provide practice recommendations for resistance training protocols in this patient population and identify characteristics of protocols with the best adherence and outcomes. With these results, we anticipate that we will gain a deeper understanding of the role of resistance training after MBS. TRIAL REGISTRATION: PROSPERO CRD42023464928; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=464928. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/49513.

Progressive multifocal leukoencephalopathy without overt immunosuppression.

Progressive multifocal leukoencephalopathy (PML) is a central nervous system disease caused by the human polyomavirus 2 that usually occurs in a setting of immunodeficiency. PML without overt immunosuppression is considered a rare occurrence but has been described in multiple previous case reports and series. Its prevalence, overall frequency, and prognosis are largely unknown. This is a single-center retrospective review of all University of Florida cases with the ICD10 PML diagnosis code (A81.2). PML without overt immunosuppression was defined as absence of human immunodeficiency virus (HIV) infection, hematological malignancy, immunomodulatory/-suppressive medications, autoimmune conditions with a propensity for PML (sarcoidosis, systemic lupus erythematosus). Cases that did not fulfill criteria for clinically or histologically definite PML were excluded. Of 52 patients with the ICD10 code A 81.2, 17 fulfilled definite diagnostic criteria for PML. Overt immunosuppression was identified in 15/17 (88.2%) cases (10/17 (58.8%): human immunodeficiency virus; 5/17 (29.4%): immunomodulatory/-suppressive medication). Two/seventeen (11.8%) cases were consistent with PML without overt immunosuppression. Possible contributing factors were a preceding dog bite and mild hypogammaglobulinemia M (39 mg/dL) in case 1 and significant alcohol use without evidence for liver disease in case 2. Both cases were fatal within 6 (case 1) and 2 (case 2) months. The results suggest that PML without overt immunosuppression may be more common than previously described. Therefore, PML should be considered even in the absence of overt immunosuppression if clinical and radiographic findings are suggestive of the diagnosis.

Oral Mucosal Lesions - A Study of 369 Cases.

Background: Diagnosing and treating oral cavity lesions is a challenging task for most of the clinicians due to similar symptoms and clinical appearances. Frequently, histopathology and immunohistochemistry aid in making the diagnosis. Objectives: The objectives were to describe the clinical features, and histopathological features and systemic association in patients with oral mucosal lesions (OML). Materials and Methods: A cross-sectional descriptive study was undertaken at a tertiary care centre in patients with OML. A total of 369 cases with OML were included in the study. Results: Males constituted 61.78% of the cases. History of habits such as tobacco, gutka chewing, smoking, and alcohol was given by 32.25%, 29.81%, 26.56%, and 11.38% of cases, respectively. Common symptoms were soreness, burning sensation, oral pain and ulcers. Both oral and cutaneous involvement was seen in 17.89% of cases. Oral lichen planus (oral LP) constituted largest group of patients (21.96%) wherein reticulate type was the most frequent type and buccal mucosa was the commonest site. Oral carcinomas constituted 20.33% of cases followed by infective etiology (11.92%), vesiculobullous group of diseases (10.30%), aphthous stomatitis (8.94%), premalignant lesions (7.05%) such as leukoplakia (3.80%) and submucous fibrosis (2.44%). Histopathology was done in 209 cases. Clinico-histopathological correlation was seen in oral LP (90.27%), oral pemphigus (82.35%), and malignancies (98.66%). Conclusion: Oral LP formed the largest group of cases followed by Oral squamous cell carcinoma (SCC). Several rare conditions, such as Melkersson-Rosenthal syndrome and blue rubber bleb nevus syndrome were also a part of the study. Thorough clinical and histopathological examination in this diverse group of diseases clinches the diagnosis.

Standard clinical and imaging-based small vessel disease parameters associated with mild stroke versus non-mild stroke.

Background: Mild stroke has variable outcomes, and there is an ongoing debate regarding whether the administration of thrombolytics improves outcomes in this subgroup of stroke patients. Having a better understanding of the features of mild stroke may help identify patients who are at risk of poor outcomes. Objective: The objective of this study is to evaluate the association of clinical and imaging-based small vessel disease features (white matter hyperintensities and cerebral microbleeds) with stroke severity and clinical outcomes in patients with mild stroke. Methods: In this retrospective study, mild stroke was defined as a National Institute of Health stroke scale (NIHSS) score <5. Clinical, laboratory and imaging data were compared between patients with mild stroke versus non-mild stroke (NIHSS≥5). Multivariate logistic regression analysis was performed to identify predictors of mild stroke and poor discharge outcome. Results: Among 296 patients included in the study, 131 patients (44%) had mild stroke. On multivariate analysis, patients with mild stroke were three times more likely to have sensory symptoms [odds ratio (OR) = 2.9; 95% confidence interval (CI) = (1.2-6.8)] and four times more likely to have stroke due to small vessel disease (OR = 3.7; 95%CI = 1.4-9.9). Among patients with mild stroke, higher age (OR = 1.1; 95%CI = 1.02-1.1), presence of cerebral microbleed (OR = 4.5; 95%CI = 1.5-13.8), vertigo (OR = 7.3; 95%CI = 1.2-45.1) and weakness (OR = 5.0; 95%CI = 1.2-20.3) as presenting symptoms were more likely to have poor discharge outcome. Conclusion: Sensory symptoms and stroke due to small vessel disease are more common in mild stroke than non-mild stroke. Among patients with mild stroke, presence of cerebral microbleeds on imaging and symptoms of muscle weakness are associated with poor discharge outcome. Larger studies are needed to assess the impact of cerebral microbleed on mild stroke outcomes and risk stratify the benefit of thrombolytics in this group.

A 40-Year-Old Woman With COVID-19 and Bilateral Vision Loss.

Mucormycosis is a fast-spreading angioinvasive fungal infection with a very high mortality rate. It is associated with immunodeficiency, diabetes mellitus, iron overload, stem cell transplantation and the use of steroids. As cultures and histopathological biopsy may have low yield in invasive fungal infections, new generation sequencing of cfDNA (cell free deoxyribonucleic acid) has become a cornerstone for diagnosis. Over the past 18 months, increasing reports of COVID-19 associated Mucormycosis have emerged, most specifically in India and other nearby developing countries. Awareness and knowledge of this newly discovered association is of high importance and clinical relevance as the global COVID-19 pandemic continues. Herein, we present a case of a patient who was treated with steroids for COVID-19 in the outpatient setting and presented with unilateral periorbital pain and blurry vision. She progressively developed bilateral vision loss, fixed bilateral mydriasis, ophthalmoplegia and coma. Imaging findings included leptomeningeal, vascular, and subcortical enhancement accompanied with multifocal infarction. Subsequent biopsy of the paranasal sinuses revealed broad type fungal elements and cfDNA sequencing identified the pathogen as Rhizopus species. She was treated with intravenous amphotericin B, but succumbed to the infection.

Rituximab in Refractory Myositis and Acute Neuropathy Secondary to Checkpoint Inhibitor Therapy.

Checkpoint inhibitor immunotherapies have been one of the latest advances through the last decade in the treatment of various cancers. As their use is increasing so is the knowledge of their complications which can affect various organ systems including the central and peripheral nervous systems. Management of these complications requires stopping the offending agent and in some cases treating with immunosuppressive agents like intravenous steroids. Physicians can face challenging situations if patients are unresponsive to steroids, intravenous immunoglobulins (IVIG), and plasmapheresis (PLEX). There are no formal guidelines to help in the management of such patients.  We present an 85-year-old male with a past medical history of renal cell carcinoma status post nephrectomy who was admitted with diplopia, eyelid ptosis, dysphagia, dysphonia, dyspnea, and generalized weakness. He was started on nivolumab and ipilimumab 10 days prior to presentation. Laboratory studies showed an elevated erythrocyte sedimentation rate, C-reactive protein, and creatine phosphokinase, and an unrevealing lumbar puncture. Acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) antibodies were negative. Electromyography and nerve conduction studies showed axonal and demyelinating sensorimotor neuropathy with no significant decrement on 3 Hz repetitive stimulation. Thyroid function tests were concerning for thyroiditis and anti-thyroid peroxidase antibodies were positive. Together, these findings led to the diagnosis of refractory myositis and acute neuropathy along with autoimmune thyroiditis from nivolumab and ipilimumab immunotherapy. His symptoms were unresponsive to a 5-day course of steroids, intravenous immunoglobulins, and plasmapheresis. He was then started on rituximab with significant improvement in ptosis, dysphagia, dysphonia, and proximal weakness. Immune checkpoint inhibitors (ICI) are associated with an increased risk for the development of various autoimmune conditions. Treatment involves discontinuation of the offending drug and initiation of immunosuppressive therapy. This case is interesting as it demonstrates the importance of the awareness of the neurological complications of the checkpoint inhibitor therapies and the beneficial role of rituximab in patients who are unresponsive to initial immunosuppressive therapies including steroids, IVIG, and PLEX.

Management of Cavernous Sinus Thrombosis Following Herpes Zoster Ophthalmicus.

Herpes zoster opthalmicus (HZO) is the reactivation of latent varicella zoster virus (VZV) within the ophthalmic branch of the trigeminal ganglion (V1). Common complications are postherpetic neuralgia and vasculopathy. Here, we report a rare case of a 47-year-old female presenting with HZO and aseptic cavernous sinus thrombosis (CST). Early screening for rare and deadly complications such as CST using CT cerebral venography (CTV) and magnetic resonance venography (MRV), as was done, is crucial to detection at earlier stages when intervention is most effective. Anticoagulation therapy was promptly started, and the patient's symptoms continued to improve during the hospital stay.

Clinical and Imaging Features Associated with the Utilization of Comfort Measures Only in Acute Ischemic Stroke.

Objectives: Up to 10% of acute ischemic stroke (AIS) patients can die in the first 30 days. Older age and a higher National Institutes of Health Stroke Scale (NIHSS) score are associated with transition to comfort measures only (CMO) in AIS. There are insufficient data on specific stroke etiology, infarct location, or vascular territory for the association of AIS with the use of CMO. We therefore evaluated the clinical and imaging factors associated with utilization of CMO and their outcomes. Methods: AIS patients seen in an academic comprehensive stroke center in the United States between July 1, 2015, and June 30, 2016, were subgrouped based on the use of CMO orders (CMO vs. non-CMO) during hospitalization. Clinical, laboratory, and imaging data were analyzed. Multivariable logistic regression analysis was performed, adjusting for pertinent covariates. Results: The study consisted of 296 patients, 27 (9%) patients were transitioned to CMO. Compared with non-CMO patients, those with CMO were older (mean ± standard deviation: 66 ± 15 vs. 75 ± 11 years, p = 0.002). Hemorrhagic transformation of AIS was more likely in CMO (17% vs. 41%, p = 0.0030) compared with non-CMO patients. On multivariate analysis, severe stroke measured by the NIHSS score (odds ratio [OR] = 1.2; 95% confidence interval [CI] = 1.1-1.4), infarction of the insular cortex (OR = 12.9; 95% CI = 1.4-118.4), and presence of cerebral edema with herniation (OR = 9.4; 95% CI = 2.5-35.5) were associated with transition to CMO. Conclusions: The presence of severe stroke, infarction of the insular cortex, and cerebral edema with herniation were associated with utilization of CMO in AIS. Impairment of multiple neurological functions served by the insular cortex could play a role in transition to CMO.

Current trends in U.S. general surgery practice consolidation.

BACKGROUND: Consolidation of physician practices is well-documented in recent years, yet minimal data exist regarding consolidation in general surgery. This study evaluates current trends in general surgery practice consolidation. METHODS: Data were obtained through the CMS Physician Compare database. Surgeons and practices were categorized by size, and trends were analyzed using the Cochran-Armitage test. Data were stratified by US region. RESULTS: From 2012 to 2020, practicing general surgeons increased from 20,044 to 20,637 (+3%). Unique general surgery practices declined from 8178 to 6489 (-21%). The percentage of surgeons in practices of 1 or 2 declined from 19% to 12%, while surgeons in groups of 500 or more grew from 20% to 31%. Tests for trends towards consolidation at both the individual surgeon and unique practice levels were significant (p < .001). The Midwest region demonstrated the highest degree of consolidation. CONCLUSION: Consistent with trends in medicine overall, general surgery is experiencing substantial practice consolidation.

Nonepileptic, Stereotypical, and Intermittent Symptoms After Subdural Hematoma Evacuation.

Transient neurological deficits can occur in the setting of subdural hemorrhages with subsequent unremarkable electrodiagnostic and radiological evaluation. This scenario is rare and can be difficult for physicians to interpret. These transient neurological deficits are thought to result from relative ischemia, secondary to a lesser-known concept known as cortical spreading depolarization. These transient neurological deficits are thought to result from relative ischemia, secondary to a lesser-known concept known as cortical spreading depolarization, which may present clinically as nonepileptic, stereotypical, and intermittent symptoms (NESIS). In these instances, patients are often misdiagnosed as epileptics and committed to long-term antiseizure drugs. We present a 51-year-old patient developing acute global aphasia following the evacuation of a subdural hematoma, with no significant findings on laboratory, microbiological, electrodiagnostic, or radiological evaluation. The patient experienced spontaneous improvement and returned to baseline in the subsequent weeks. Increased awareness of NESIS as a cortical spreading depolarization phenomenon can improve patient care and prevent both unnecessary, extended medical evaluations and therapeutic trials.

P022 Biologic Therapy and Therapeutic Drug Monitoring in Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD). Patients with concomitant PSC-IBD are at higher risk for IBD-related complications including dysplasia and malignancy, however the typical clinical IBD course is less severe. The aim of this study was to identify the prevalence of biologic use and therapeutic drug monitoring (TDM) in a cohort of PSC-IBD patients. METHODS: Retrospective analysis of patients with PSC-IBD on biologic therapy who underwent TDM from Jan. 2018 to Aug. 2020 at the University of Virginia. Demographic data including age, disease duration, and comorbidities were recorded. IBD categorizations were recorded according to the Montreal Classification. Treatment outcomes including therapy changes after TDM were obtained. RESULTS: A total of 157 patients with PSC-IBD were identified. Of these, 29 patients (19%) were treated with biologic therapy during the study period. 13 patients underwent reactive TDM due to primary or secondary loss of response and one patient underwent proactive TDM during the study period. Median duration of IBD in this group was 9 years, and the median duration of concomitant PSC-IBD was 5.8 years. 20 TDM tests were obtained in these 14 total patients. Sub-therapeutic drug levels were found in 12 tests among 8 patients, and 3 showed detectable anti-drug antibodies. 8 showed appropriate trough levels. TDM resulted in a change to IBD therapy (i.e., dose escalation, change in biologic therapy used, or addition of IBD medication) in 17 out of 20 tests. CONCLUSION: Herein we describe epidemiologic data of biologic use in PSC-IBD patients at an academic center. PSC-IBD classically follows a less severe clinical presentation and course. However, our study demonstrates that a subset of PSC-IBD patients exist which require biologic therapy and follow a more refractory clinical trajectory. In this subset, TDM showed a high incidence of sub-therapeutic trough levels and anti-drug antibodies, leading to a change in therapy in 85% of TDM instances. Larger studies are recommended to better understand this unique subset of PSC-IBD patients.