The risks of rejection vs. infection: Ramsay Hunt syndrome, Gradenigo syndrome, and varicella meningoencephalitis in a heart transplant patient.

Background: Orthotopic heart transplant (OHT) recipients are at increased risk for varicella zoster reactivation, and severe complications may arise due to their immunosuppressive regimens. Managing immunosuppression in acute infection is difficult, and specific guideline recommendations or evidence from the literature are lacking. However, patient care must involve weighing the risk of transplant rejection with the consequences of worsening infection. Case summary: An OHT patient with a history of multiple episodes of acute rejection, latent varicella zoster virus (VZV) infection, and recent completion of anti-viral prophylaxis presented with unilateral facial droop and pain, abducens nerve palsy, crusting facial rash, and ear swelling. Imaging revealed necrotizing otitis externa, with associated otitis media, and petrous apicitis concerning for Gradenigo syndrome. A VZV-positive viral panel confirmed our suspicion for Ramsay Hunt syndrome (RHS). The patient's mentation continued to decline, and subsequent lumbar puncture also revealed VZV meningoencephalitis. The patient's mycophenolate mofetil (MMF) was suspended, with continuation of tacrolimus, and initiation of intravenous acyclovir. The patient demonstrated gradual resolution of his infection, without developing any signs of acute rejection. Discussion: Varicella zoster virus reactivation is common in OHT patients, particularly when viral prophylaxis is discontinued; however, cardiologists should be aware of the rarer manifestations that can manifest in these immunocompromised patients. This is the first documented case of simultaneous RHS, Gradenigo syndrome, and VZV meningoencephalitis in any patient, regardless of transplant status. We demonstrate that even in patients at very high risk of rejection, MMF can be safely discontinued and host immunity maintained with temporary tacrolimus monotherapy.

Clinical characteristics of blue rubber bleb nevus syndrome in adults: systematic scoping review.

BACKGROUND: Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular anomaly mainly affecting the skin, central nervous system and gastrointestinal tracts. Its clinical presentation and characteristics in adult patients are unclear. AIM: To clarify the characteristics of BRBNS in adult patients with a focus on gastrointestinal symptoms. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including 'Blue rubber bleb nevus syndrome' from their inception to 28 December 2021. RESULTS: Ninety-nine articles, including 3 observational studies and 101 cases from case reports and series, were included. Observational studies were consistently with small sample sizes, and there was only one prospective study to show the effectiveness of sirolimus in BRBNS. Common clinical presentations included anemia (50.5%) and melena (26.5%). While skin findings were known to be representative of BRBNS, only 57.4% had known vascular malformation. The diagnosis was primarily made clinically, with only 1% being diagnosed with BRBNS through genetic sequencing. Distribution of BRBNS-related lesions were variable, but predominantly oral (55.9%), followed by small bowel (49.5%), colorectal (35.6%) and stomach (26.7%) vascular malformations. CONCLUSION: While it has been underrecognized, adult BRBNS could be a culprit for refractory microcytic anemia or occult gastrointestinal bleeding. Further studies are critical to establish a uniform understanding of diagnosis and treatment for those with adult BRBNS. The utility of genetic testing in adult BRBNS diagnosis and the patient characteristics that may benefit from sirolimus, a potentially curative agent, remain to be clarified.

Collagenous Gastritis Is an Underdiagnosed Cause of Anemia and Abdominal Pain: Systematic Scoping Review.

BACKGROUND: Collagenous gastritis (CG) is a rare disease characterized by infiltration of the lamina propria with mononuclear cells and subepithelial deposition of collagen. Due to its nonspecific presentation, it is often misdiagnosed. The clinical characteristics, endoscopic, and histopathologic features, and treatment outcomes of CG have not been well defined. AIMS: We aim to summarize the existing evidence of CG. METHODS: According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with keywords including "collagenous gastritis" and "microscopic gastritis" from the inception of these databases to August 20, 2022. RESULTS: 76 Articles, including nine observational studies, and 67 case reports and series were included. There were 86 cases of collagenous colitis in the final analysis. Most patients presented with anemia (61.4%), followed by abdominal discomfort (60.5%), diarrhea (25.3%), and nausea/vomiting (23.0%). While 60.2% had gastric nodularity on endoscopy, erythema or erosions (26.1%) were also common, as well as normal findings (12.5%). 65.9% of histopathologic findings included subepithelial collagen bands, and 37.5% had mucosal inflammatory infiltrates. Common treatments employed were iron supplementation (42%), followed by PPI (30.7%), prednisone (9.1%), and budesonide (6.8%). Clinical improvement was seen in 64.2%. CONCLUSION: This systematic review summarizes the clinical characteristics of CG. Further studies to establish clear diagnostic criteria and identify effective treatment modalities of this less-recognized entity are needed.

Perioperative Complications in Patients over 70 Years of Age following Simultaneous Bilateral Total Knee Arthroplasty.

Single-stage bilateral total knee arthroplasty (ssBTKA) can be used for patients presenting with bilateral arthritis and may result in fewer systemic and wound complications compared with two, independent procedures. However, the safety of ssBTKA in the elderly remains controversial. Therefore, the purpose of this study was to compare early complications and transfusion rates following ssBTKA in patients ≤ 70 years old or > 70 years old. This retrospective chart review of 313 consecutive patients undergoing ssBTKA included 174 patients ≤ 70 years old and 139 patients > 70 years old. Perioperative variables and postoperative complications were compared with univariate analyses between age groups. Multivariate analyses were performed to determine risk factors for developing perioperative complications and transfusions. Compared with patients ≤ 70, patients > 70 had significantly lower body mass index (p < 0.001) and were more commonly female (p = 0.024). Although wound (p > 0.12) and systemic complications (p > 0.54) were similar, 23% of patients > 70 required transfusion compared with only 8% of patients ≤ 70 (p < 0.001). Patients with preoperative anemia (p < 0.001), age > 70 (p = 0.002), or diabetes mellitus (p = 0.007) were at 5.7, 3.3, and 2.9 times greater risk for requiring a transfusion, respectively. Patients > 70 undergoing ssBTKA have a similar complication profile to patients ≤ 70 years old, suggesting age should not be an absolute exclusion criterion for ssBTKA. However, the risk of transfusion was significantly higher in those > 70, despite lower tourniquet times. Treatment of preoperative anemia may decrease the risk of transfusion and could provide adequate safety for patients > 70 to undergo ssBTKA by an experienced surgeon.

Hypoglycemia Is Associated With Worse Outcomes in Patients With Cholangitis Despite Undergoing Endoscopic Retrograde Cholangiopancreatography.

Background Hypoglycemia has been associated with poorer outcomes in hospitalized patients undergoing surgical interventions. In cholangitis, endoscopic retrograde cholangiopancreatography (ERCP) is often a critical adjunct to surgery, capable of diagnosing and treating various biliary and pancreatic pathologies. While technically less invasive than surgery, the effect of hypoglycemia on clinical outcomes of patients with cholangitis undergoing ERCP has not been elucidated. Methodology Data were extracted from the National Inpatient Sample (NIS) database from 2016 to 2019. Using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, patients diagnosed with cholangitis and underwent ERCP were identified. Baseline demographic data, comorbidities, in-hospital mortality, hospital charges, and hospital length of stay (LOS) were extracted and compared based on the presence or absence of hypoglycemia. Statistical analysis was done using t-test and chi-square analyses. A multivariate analysis for the mortality odds ratio (OR) was calculated to adjust for possible confounders. Results A total of 256,540 patients with cholangitis who underwent ERCP were identified, and 2,810 of them had hypoglycemia during their hospitalization. The mean age of the hypoglycemia group was 64.41 years. Most patients were females (54%) and whites (57%). More patients in the hypoglycemia group had a history of alcoholism and congestive heart failure (CHF). Hypoglycemia was associated with higher odds of in-hospital mortality (OR = 6.71, confidence interval (CI) = 5.49-8.2; p < 0.0001). In addition to hypoglycemia, age >65 years, non-white race, and CHF were independently associated with higher mortality. Moreover, patients with hypoglycemia had higher total hospital charges ($87,147 vs. $133,400; p < 0.0001) and a significant increase in the LOS (9.7 vs. 6.7 days; p < 0.0001). Conclusions Previous studies in the surgical literature have linked hypoglycemia to increased incidence of atrial fibrillation, usage of mechanical ventilation, and application of circulatory support. Hypoglycemia may also affect the metabolism of the heart, leading to myocardial ischemia and malignant arrhythmias. However, it is unclear if hypoglycemia represents a proxy for the severity of patient illness as septic shock and renal insufficiency are common etiologies that may strongly impact mortality. Therefore, careful glycemic control during hospitalization should be practiced as hypoglycemia serves as a poor prognostic indicator that should not be overlooked.

Clinical Characteristics and Outcomes of Gastritis Associated With Immune Checkpoint Inhibitors: Scoping Review.

Among immune-related adverse events associated with immune checkpoint inhibitors, immune-mediated gastritis (IMG) has been rarely described in the literature and has not yet been well characterized. This scoping review aimed to characterize IMG in terms of precipitating agents, clinical presentations, and prognosis. After the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "gastritis," "immune checkpoint inhibitor," and "immune-related adverse event" from their inception to December 28, 2021. Twenty-two articles, including 5 observational studies and 17 case reports and case series, were included. Nivolumab, pembrolizumab, and combination therapy with those and cytotoxic T-lymphocyte-associated antigen-4 inhibitor (ipilimumab) were commonly used in those with IMG. 59.8% had epigastric pain, and 50% had erosive gastritis. 87.5% had Common Terminology Criteria for Adverse Events (CTCAE) grade 3 gastritis, and 91.2% received corticosteroids. Recurrence was noted in 16.7%, and only 1 expiration was noted. 4.3% had positive helicobacter pylori and cytomegalovirus from the gastric specimen. Similar to immune-related colitis, patients with IMG may have a favorable prognosis with a better response to immune checkpoint inhibitors if treated appropriately. The diagnosis of IMG is made by exclusion, and a thorough workup is necessary to rule out concurrent helicobacter pylori and cytomegalovirus involvement. Further studies are critical for a better understanding of this complication.

Clinicopathological characteristics of gastric IgG4-related disease: Systematic scoping review.

BACKGROUND AND AIM: Gastric IgG4-related disease (IgG4-RD) can mimic malignancy, submucosal tumors (SMT), and ulcers, leading to over-triage and unnecessary medical interventions such as gastrectomy. The variability in the clinicopathological presentation of IgG4-related disease is not yet well defined, posing a diagnostic challenge. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "gastritis," "stomach," "gastrointestinal stromal tumor," and "IgG4-RD" from their inception to December 28, 2021. RESULTS: Thirty-nine articles, including 2 observational studies and 42 cases, were included in the systematic review. While bottom-heavy lymphoplasmacytic mucosal infiltration is a characteristic finding of gastric IgG4-RD, it was only present in less than half of the patients in the observational studies. Patients with gastric IgG4-RD were more likely to be diagnosed with gastrointestinal stromal tumor (GIST), gastric cancer, or peptic ulcer disease and their clinical course involved resection (51.3%) or even gastrectomy. Diagnosis of gastric IgG4-RD was most frequently made by post-operative pathological analysis. CONCLUSION: This systematic review summarizes the current understanding of the characteristics of gastric IgG4-RD. Increased awareness of gastric IgG4-RD as a differential diagnosis of gastric SMT or ulcers among clinicians is crucial in order to reduce unnecessary high-risk, invasive interventions.

FOLFOXIRI in Pregnant Women with Colorectal Cancer: A Case Report and Review of the Literature.

Colorectal cancer (CRC) in pregnancy is rare and often presents at a late stage due to the masking of signs by pregnancy. A typical chemotherapeutic regimen for stage III and IV CRC comprised 5-Fluorouracil (5-FU) and oxaliplatin. The treatment of CRC during pregnancy is complicated owing to the potential risk of teratogenicity with chemotherapy, especially in the first trimester. Data suggest that the administration of chemotherapy beyond the first trimester may be relatively safe. Previous reports have shown success with the use of FOLFOX (folinic acid, 5-FU, oxaliplatin) and FOLFIRI (folinic acid, 5-FU, irinotecan) during pregnancy. Moreover, neoadjuvant FOLFOXIRI (folinic acid, 5-FU, oxaliplatin, irinotecan) resulted in improved outcomes when compared to standard preoperative chemoradiotherapy in the treatment of locally advanced and metastatic CRC. The use of FOLFOXIRI in pregnancy is not currently documented, and therefore, the outcomes of using this chemotherapeutic regimen are unclear. The aim of this case report was to demonstrate the use of FOLFOXIRI in pregnancy. A retrospective chart review was performed to assess the clinical course and fetal outcome of 2 patients presented in this case report. FOLFOXIRI was initiated in two pregnant women with nonmetastatic and metastatic CRC, resulting in successful delivery of healthy infants. FOLFOXIRI is an effective chemotherapy regimen for the treatment of advanced CRC and may be used during the second and third trimesters of pregnancy.

Congestive Heart Failure Is Associated With Worse Outcomes in Patients With Ischemic Colitis: A Nationwide Study.

INTRODUCTION: Ischemic colitis (IC) results from compromised blood flow to the colon. Risk factors include atrial fibrillation (A.Fib), peripheral artery disease (PAD), coronary artery disease (CAD), and congestive heart failure (CHF). However, few studies compared the mortality rate and colectomy between patients with IC with CHF and IC alone. OBJECTIVE: We aim to investigate the possibility of worse outcomes in patients with IC and CHF compared to IC alone. METHODOLOGY: Using the National Inpatient Sample database from 2016 to 2019, we obtained baseline demographic data, total hospital charge, rate of colectomy, length of hospital stay (LOS), and in-hospital mortality. Data were compared using a t-test and chi-squared. Odds ratios for comorbidities including A.Fib, CAD, PAD, end-stage renal disease, chronic obstructive pulmonary disease, hyperlipidemia, hypertension, diabetes, and cirrhosis were calculated. RESULTS: 106,705 patients with IC were identified, among which 15,220 patients also had CHF. IC patients with CHF had a longer LOS (6.6 days vs 4.4 days; P<0.0001), higher total hospital charge ($71,359 vs $45,176; P<0.0001), higher mortality rate (8.5% vs 2.9%; P<0.0001), and higher colectomy rate (9.2% vs 5.9%; P<0.0001). CONCLUSION: CHF is associated with poor outcomes in patients with IC. Our study showed an increased risk of mortality and colectomy compared to patients with IC alone. The findings suggest it may be warranted to have a heightened clinical suspicion of IC in patients with CHF who present with bleeding per rectum.

Association between Mineralocorticoid Receptor Antagonist and Mortality in SARS-CoV-2 Patients: A Systematic Review and Meta-Analysis.

Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been proposed. The protective effects of mineralocorticoid receptor antagonists (MRA) against tissue fibrosis, pulmonary and systemic vasoconstriction, and inflammation have been implicated in potentially attenuating the severity of SARS-CoV-2 infection by inhibiting the deleterious effects of aldosterone. Furthermore, spironolactone, a type of MRA, has been suggested to have a beneficial effect on SARS-CoV-2 outcomes through its dual action as an MRA and antiandrogen, resulting in reduced transmembrane protease receptor serine type 2 (TMPRSS2)-related viral entry to host cells. In this study, we sought to investigate the association between MRA antagonist therapy and mortality in SARS-CoV-2 patients via systematic review and meta-analysis. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE databases were searched for studies that reported the incidence of mortality in patients on MRA with SARS-CoV-2 infection. Pooled odds ratio (OR) and 95% confidence interval (CI) of the outcome were obtained using the random-effects model. Five studies with a total of 1,388,178 subjects (80,903 subjects receiving MRA therapy) met the inclusion criteria. We included studies with all types of MRA therapy including spironolactone and canrenone and found no association between MRA therapy and mortality in SARS-CoV-2 infection (OR = 0.387, 95% CI: 0.134-1.117, p = 0.079).

Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: What We Already Know.

Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP) resulting in significant morbidity and occasional mortality. Post-ERCP pancreatitis (PEP) has been recognized since ERCP was first performed, and many studies have shown a consistent risk that must be balanced against the many benefits of this procedure. This review will discuss the pathogenesis, epidemiology, potential risk factors, and clinical presentation of PEP. Moreover, it will discuss in detail the most recent updates of PEP prevention and management.

Prognostic Significance of Lymphocyte Infiltration and a Stromal Immunostaining of a Bladder Cancer Associated Diagnostic Panel in Urothelial Carcinoma.

We set out to expand on our previous work in which we reported the epithelial expression pattern of a urine-based bladder cancer-associated diagnostic panel (A1AT, ANG, APOE, CA9, IL8, MMP9, MMP10, PAI1, SDC1, and VEGFA). Since many of the analytes in the bladder cancer-associated diagnostic signature were chemokines, cytokines, or secreted proteins, we set out to report the stromal staining pattern of the diagnostic signature as well as CD3+ (T-cell) cell and CD68+ (macrophage) cell staining in human bladder tumors as a snapshot of the tumor immune landscape. Immunohistochemical staining was performed on 213 tumor specimens and 74 benign controls. Images were digitally captured and quantitated using Aperio (Vista, CA). The expression patterns were correlated with tumor grade, tumor stage, and outcome measures. We noted a positive correlation of seven of the 10 proteins (excluding A1AT and IL8 which had a negative association and VEGFA had no association) in bladder cancer. The overexpression of MMP10 was associated with higher grade disease, while overexpression of MMP10, PAI1, SDC1 and ANG were associated with high stage bladder cancer and CA9 was associated with low stage bladder cancer. Increased tumor infiltration of CD68+ cells were associated with higher stage disease. Overall survival was significantly reduced in bladder cancer patients' whose tumors expressed eight or more of the 10 proteins that comprise the bladder cancer diagnostic panel. These findings confirm that the chemokines, cytokines, and secreted proteins in a urine-based diagnostic panel are atypically expressed, not only in the epithelial component of bladder tumors, but also in the stromal component of bladder tumors and portends a worse overall survival. Thus, when assessing immunohistochemical staining, it is important to report staining patterns within the stroma as well as the entire stroma itself.

Meta-analysis of a 10-plex urine-based biomarker assay for the detection of bladder cancer.

A 10-plex urine-based bladder cancer (BCa) diagnostic signature has the potential to non-invasively predict the presence of BCa in at-risk patients, as reported in various case-control studies. The present meta-analysis was performed to re-evaluate and demonstrate the robustness and consistency of the diagnostic utility of the 10-plex urine-based diagnostic assay. We re-analyzed primary data collected in five previously published case-control studies on the 10-plex diagnostic assay. Studies reported the sensitivity and specificity of ten urinary protein biomarkers for the detection of BCa, including interleukin 8, matrix metalloproteinases 9 and 10, angiogenin, apolipoprotein E, syndecan 1, alpha-1 antitrypsin, plasminogen activator inhibitor-1, carbonic anhydrase 9, and vascular endothelial growth factor A. Data were extracted and reviewed independently by two investigators. Log odds ratios (ORs) were calculated to determine how strongly the 10-plex biomarker panel and individual biomarkers are associated with the presence of BCa. Data pooled from 1,173 patients were analyzed. The log OR for each biomarker was improved by 1.5 or greater with smaller 95% CI in our meta-analysis of the overall cohort compared with each analysis of an individual cohort. The combination of the ten biomarkers showed a higher log OR (log OR: 3.46, 95% CI: 2.60-4.31) than did any single biomarker irrespective of histological grade or disease stage of tumors. We concluded that the 10-plex BCa-associated diagnostic signature demonstrated a higher potential to identify BCa when compared to any single biomarker. Our results justify further advancement of the 10-plex protein-based diagnostic signature toward clinical application.