Molecular testing of cytology specimens: Issues in specimen adequacy and clinical utility.

BACKGROUND: Next generation sequencing (NGS) is standard of care for workup of many neoplasms including adenocarcinomas of the lung. Molecular testing of cytology samples is used for many types of neoplasms but the value of such testing for the selection of "first"- and "second-line" treatment protocols is incompletely understood. METHODS: Fifty-six sequentially performed cytology specimens (49 fine needle aspirates and 7 fluids) submitted for molecular analysis were reviewed by a medical oncologist to determine specimen adequacy and utility of results for therapy selection. Chart review was performed to determine availability of microsatellite instability status, tumor mutational burden, and presence of driver mutations treatable with targeted therapy in a "first"- or "second-line" application. RESULTS: Forty of 56 cases were successfully sequenced and 34% (19/56) had targetable mutations detected by NGS. Ten of these 19 cases (53%) received targeted therapy for their tumor type with five of 10 patients receiving "first-line" therapy and five (50%) "second-line" therapy. Twenty-two mutations were detected where no targeted therapy for the patient's tumor type existed but targeted therapies were available for other tumor types. Of these specimens, only one patient received treatment using protocols associated with a second tumor type. Total mutation burden and microsatellite instability status results were obtained in 29 of 56 cases (52%). CONCLUSIONS: 71% (40/56) of cytologic specimens were adequate for sequencing with 34% (19/56) demonstrating a targetable mutation and 53% of these patients receiving therapy targeted to the driver mutation of their tumor type.

Effect of radiofrequency ablation in addition to biliary stent on overall survival and stent patency in malignant biliary obstruction: an updated systematic review and meta-analysis.

OBJECTIVES: Radiofrequency ablation (RFA) is used in addition to stent placement to manage extrahepatic malignant biliary obstruction. We aimed to study the effect of RFA on overall survival (OS) and stent patency in malignant biliary obstruction. METHODS: A comprehensive literature search was performed from inception to May 2022 for all studies measuring the effect of RFA plus stents compared to stents placement only on OS and stent patency in patients with malignant biliary obstruction. We measured differences in OS, stent patency, and odds of adverse events. A random effect model was used to pool data for stent patency, OS, and adverse event. RESULTS: A total of 17 studies (14 observational and 3 RCT) containing 1766 patients were included in the analysis. The weighted pooled mean survival difference was 58.5 days [95% confidence interval (CI): 32.6-84.4, I2 = 71%] in favor of the RFA treatment group. The weighted mean difference in stent patency was better in the RFA plus stent group by 45.3 days (95% CI: 30.1-60.5, I2 = 16.4%) compared to stent only group. The pooled odds of adverse events were the same in both groups [odds ratio (OR) 1.52, 95% CI: 0.96-2.43, I2 = 59%], and no serious adverse event was seen in either group, or no death reported secondary to RFA procedure. No difference in stent patency based on procedure type, including percutaneous transhepatic cholangiography versus endoscopic retrograde cholangiopancreatography (P = 0.06), and an underline cause of bile duct obstruction was found (P = 0.261). CONCLUSION: RFA treatment, in addition to stent placement in malignant biliary obstruction, potentially improves OS and stent patency duration.

Lemierre Syndrome: A Diagnosis behind the Veil.

Lemierre syndrome (LS) is a rare, serious infection that is often misdiagnosed, as it frequently mimics common upper respiratory infections. It is even rarer for LS to be preceded by a viral infection. We share a case of LS in a young man who presented to the Emergency Department with COVID-19 viral infection followed by a subsequent LS diagnosis. The patient's condition initially worsened despite treatments for COVID-19 and was subsequently started on broad-spectrum antibiotics. He was then diagnosed with LS after blood cultures grew Fusobacterium necrophorum, and antibiotics were adjusted accordingly, resulting in improvement of symptoms. Even though LS is often recognized as a sequela of bacterial pharyngitis, preceding viral infections, including COVID-19, might be a risk factor that contributes to the development of LS.

Effect of acute kidney injury on hospital-based outcomes in patients admitted for variceal hemorrhage. Analysis of national inpatient sample database.

Introduction: Acute kidney injury (AKI) is known to be a marker of mortality in patients with cirrhosis and variceal hemorrhage. Aim: To study the effect of AKI on hospital-based outcomes in patients with variceal hemorrhage. Material and methods: We obtained data from the National Inpatient Sample for the years 2016-2018. Study inclusion criteria comprised adult variceal hemorrhage patients who also had AKI. The primary outcome of interest was in-hospital mortality. Secondary outcomes were length of stay, hospital charge, shock, blood transfusion, and ICU admission. We also determined the independent predictors of mortality in variceal hemorrhage patients using multivariate regression analysis. We used 2 different methods: multivariate logistic regression and propensity matching to adjust for confounders. Results: The number of people included in this study was 124,430, of whom 32,315 (26%) had AKI. Mortality in variceal hemorrhage patients with AKI was 30.4% in comparison to 4.8% without AKI. The presence of AKI was associated with increased odds of mortality (AOR = 8.28, 95% CI: 7.45-9.20, p < 0.01), ICU admissions (AOR = 4.76, 95% CI: 4.42-5.13, p < 0.01), blood transfusion (AOR = 1.24, 95% CI: 1.15-1.32, p < 0.01), and shock (AOR = 3.41, 95% CI 3.07-3.79, p < 0.01). The patients with AKI also had increased length of stay and hospital charges. Higher Charlson co-morbidity index, African American race, and being admitted to large sized hospital were independently associated with increased mortality. Conclusions: After analyzing the combined NIS dataset of 2016-2018, we concluded that patients admitted with variceal hemorrhage who has AKI are prone to adverse hospital outcomes.

A national study of pregnancy-related maternal and fetal outcomes in women with inflammatory bowel disease.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) among women is highest during their reproductive years and current estimates suggest that the rate of conception is low in female IBD patients. The aim of our study was to assess the burden of adverse maternal and perinatal outcomes among female IBD patients. METHODS: Using the national inpatient sample database from 2016 to 2018, we recruited all female patients above the age of 15 years admitted with a primary diagnosis of pregnancy and a secondary diagnosis of IBD. We adjusted our results for hospital and patient level variables including age, race, socioeconomic status, hypertension, diabetes mellitus, obesity, smoking, hyperlipidemia, alcohol use, and malnutrition. Multivariable regression analysis was used for analysis. RESULTS: Pregnant women with IBD had greater odds of gestational diabetes (adjusted odds ratio [AOR] 1.55, 95% confidence interval [CI] 1.04-2.3, p 0.02), hypertensive complications (AOR 1.35, 95% CI 1.06-1.72, p 0.01), and pre-term delivery (AOR, 1.41 95% CI 1.13-1.76, p 0.003). Pregnancies with co-existent IBD were associated with fetal growth restriction (AOR 1.27, 95% CI 1-1.63, p 0.04) and fetal death (AOR 3.21, 95% CI 1.72-6.00, p < 0.01). Odds of experiencing postpartum hemorrhage or large for gestational age infant were comparable to general population. Crohn's disease was independently associated with increased odds of worse maternal and fetal outcome. IBD patients had increased mean length of stay by 0.14 days and increased mean hospital charges of $2741. CONCLUSIONS: Women with IBD had greater likelihood of poor maternal and fetal outcomes and increased hospital resource utilization.

Safety of anticoagulation use for treatment of portal vein thrombosis in liver cirrhosis and its effect on hospital-based outcomes: an insight from a US nationwide database.

BACKGROUND AND AIM: Anticoagulation use for portal vein thrombosis (PVT) in patients with advanced liver disease is controversial. We investigated the effect of anticoagulation on outcomes in patients with PVT with cirrhosis. METHODS: We reviewed National Inpatient Sample data from 2016 to 2018 to identify patients with PVT. Our outcomes were in-hospital mortality, variceal bleeding, hepatic encephalopathy, acute kidney injury (AKI), hepatorenal syndrome (HRS), spontaneous bacterial peritonitis (SBP), sepsis and hospital resource utilisation. RESULTS: We included 60 505 patients with PVT, out of whom 6.63% (4015) were on anticoagulation. The overall mortality in the anticoagulation group was 2.12% compared with 9.72% in the no anticoagulation group. The adjusted odds of mortality were low in the anticoagulation group (adjusted OR (AOR) 0.27, 95% CI 0.15 to 0.46, p<0.001). Patients on anticoagulation had 29% lower odds of variceal bleeding (AOR 0.71, 95% CI 0.53 to 0.96, p=0.03). Lower odds of HRS (AOR 0.56, 95% CI 0.37 to 0.85, p=0.01) and AKI (AOR 0.57, 95% CI 0.48 to 0.69, p<0.001) were also seen in the anticoagulation group. Patients in the anticoagulation group also showed lower odds of SBP (AOR 0.62, 95% CI 0.43 to 0.89, p=0.01) and sepsis (AOR 0.57, 95% CI 0.35 to 0.93, p=0.03). Anticoagulation use resulted in shorter hospital stay by 1.15 days (adjusted length of stay -1.15, 95% CI -1.51 to -0.79, p<0.001). The mean difference in total hospital charges between the anticoagulation and the no anticoagulation group was -$20 034 (95% CI -$27 077 to -$12 991, p<0.001). CONCLUSION: Our analysis found that anticoagulation use is safe and associated with better outcomes in patients with PVT with advanced liver disease.

Burden of depression and anxiety among patients with inflammatory bowel disease: results of a nationwide analysis.

PURPOSE: The burden of psychiatric disorders is on a rise in inflammatory bowel disease (IBD) patients which has shown to effect medication compliance and overall clinical outcomes. We studied the prevalence of depression and anxiety in IBD patients when compared to individuals with other chronic medical conditions. METHODS: This is a retrospective cohort study using the United States national inpatient sample of 2016 to 2018. We identified patient encounters with a diagnosis of IBD. Our primary outcome was prevalence of depression and anxiety in IBD patients when compared to general adult population with other chronic medical conditions. We further studied these outcomes in subgroups of patients with ulcerative colitis and Crohn's disease. RESULTS: A total of 963,619 patient encounters were identified with the diagnosis of IBD between 2016 and 2018, of them 162,850 (16.9%) had depression and 201,685 (20.9%) had anxiety. The prevalence of depression and anxiety was significantly higher in IBD patients in comparison to general population, (16.9% vs 12.3%) and (20.9% vs 15%) respectively (p < 0.001). Association of depression and anxiety was also higher in IBD patients when compared to patients with other chronic conditions like diabetes, metastatic cancer, and coronary artery disease. Crohn's disease and ulcerative colitis were independently associated with increased odds of depression and anxiety and these results were statistically significant (p < 0.001). CONCLUSIONS: IBD is associated with increased prevalence of depression and anxiety when compared to general population. Association of these psychiatric illnesses with IBD is significantly higher when compared to other chronic medical conditions.

Does the Route of Cocaine Use Affect the Mortality and Outcomes of Cocaine-Induced Intestinal Ischemia? A Systematic Review.

Intestinal ischemia results from diminished perfusion of the colon resulting in tissue hypoxia. Anecdotal reports suggest that cocaine-induced intestinal ischemia has the highest mortality and longer length of stay among the vasoconstrictors. The present study aimed to summarize the available studies in the literature to assess the effect of routes of consumption on the outcomes of cocaine-induced intestinal ischemia. We conducted a systematic search of MEDLINE from inception through October 2019. Studies of cocaine-induced intestinal ischemia were included if data were available on comorbidities, mortality, and hospital length of stay (LOS). The study's primary outcomes were mortality and need for surgery, while secondary outcomes included the hospital length of stay, LACE index, and hospital score. Statistical tests used included linear and binary logistic regression. STATA 2015 was used, and P < 0.05 was statistically significant. Of the 304 studies, 8 case series and 45 case reports (n = 69 patients) met the inclusion criteria. Different routes of cocaine use had similar mortality odds and the need for surgery for intestinal ischemia. Hospital LOS showed significant difference among the subgroups. Readmission scores (LACE and hospital score) were higher for intravenous and smoking than ingestion and intranasal use (P < 0.05). In conclusion, different routes of cocaine use appear to have similar mortality odds for intestinal ischemia, which vary significantly among the different routes of cocaine consumption for the length of stay and readmission scores. Prompt recognition of the route of cocaine use is vital to improve the outcome. Large-scale and well-designed observational studies are needed to investigate this topic further.

Does Performing Endoscopy Sooner Have an Impact on Outcomes in Patients With Acute Nonvariceal Upper Gastrointestinal Hemorrhage? A Systematic Review.

Background Endoscopy is the cornerstone for the diagnosis and treatment of nonvariceal upper gastrointestinal bleeding. Regarding the management of nonvariceal bleeding, the administration of crystalloid solution and proton pump inhibitors before endoscopy is well established, but the optimal timing of endoscopy has been a matter of debate and a subject of many investigational studies. The need for urgent endoscopy arises to provide prompt redress to acute bleeding, decrease the length of stay, and lower mortality from ongoing bleeding. Objective This study aimed to determine if endoscopy performed within 24 hours of presentation improves outcomes in terms of mortality, hospital length of stay, and rebleeding in individuals presenting with nonvariceal upper gastrointestinal bleed with any risk. Methodology We performed a systematic review of two large databases (PubMed and Google Scholar) to incorporate all studies published after 2000. We included studies with nonvariceal upper gastrointestinal bleeding and excluded those reporting variceal gastrointestinal hemorrhage. Results We reviewed eight studies that qualified after meeting our inclusion and exclusion criteria. We divided these studies into three separate groups based on the timing of endoscopy. Only two studies found a difference in mortality that was statistically significant in patients who underwent endoscopy within 24 hours of presentation. One study showed lower mortality in a patient who underwent urgent endoscopy, but it did not reach statistical significance. Other studies did not show any statistical difference in mortality, hospital length of stay, and rebleeding rates. The studies showed conflicting evidence on the amount of blood transfusion, though urgent endoscopy was found to be difficult in few studies due to blood obscuring the lesion. Conclusions While data suggest that there is a potential benefit in performing endoscopy sooner, there is no concrete evidence to point to a particular time range. Before performing endoscopy, the American Society for Gastrointestinal Endoscopy (2012) recommends adequate resuscitation with crystalloid solutions, blood transfusions, and antisecretory and prokinetic agent therapy. More investigational studies are needed to formulate a time-sensitive flow sheet to approach endoscopy in patients with nonvariceal upper gastrointestinal bleeding. A strict criterion is also needed to delineate patients into low-risk and high-risk groups. Doing so would provide a systematic approach to help with mortality, rebleeding, and healthcare resource utilization.

Encephalitis Associated With Hemophagocytic Lymphohistiocytosis Secondary to Immune Checkpoint Inhibitors: An Unfamiliar Spin-Off.

Checkpoint inhibitors (CPI) have become mainstream in standard therapy in various tumors, especially in malignant melanoma. Despite their widespread beneficial effects, these inhibitors are also notorious for immune-related adverse events (irAEs). Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation. We report a case of a 33-year-old male having a history of metastatic melanoma on immunotherapy (status post two cycles of ipilimumab/nivolumab) admitted for persistent fever and elevated liver enzymes. Additional work showed anemia, thrombocytopenia, hypertriglyceridemia, and hyperferritinemia which meet the diagnostic criteria of histiocyte society HLH-2004. The patient was effectively treated with oral prednisone. Moreover, further complications encompassed slurred speech, word-finding difficulties, ataxia, and lower extremity hyperreflexia concerning for autoimmune encephalitis. He was treated with high-dose IV methylprednisolone (1 gram/day for 3 days) with improvement in symptoms. Autoimmune encephalitis associated with HLH can be fatal - high-dose IV methylprednisolone should be considered, but this avenue still needs to be explored.

Pravastatin-Induced Acute Pancreatitis: A Case Report and Literature Review.

Pancreatitis is inflammation of pancreas associated most commonly with chronic alcoholism and gallstones. Other less common causes of pancreatitis are hyperlipidemia, infections, surgery, trauma, post endoscopic retrograde cholangiopancreatography, and drugs. Drugs are now increasingly recognized as a cause of pancreatitis, and high suspicion and exclusion of other most common causes is required before considering drug-induced pancreatitis. There are few case reports of acute pancreatitis in the literature after statin use, but out of these, only 3 are after starting pravastatin. We are reporting a case of 49-year-old male who presented with nausea, vomiting, and abdominal pain. His laboratory findings were significant for lipase more than 10 000 on admission, and computed tomography scan of abdomen was showing peripancreatic fat stranding and inflammation. After exclusion of most common causes of pancreatitis, pravastatin was found probable culprit for his symptoms, which he started taking 2 weeks ago. We also reviewed the literature on statins-induced acute pancreatitis. With increased uses of statins, physician need to be vigilant to suspect statins as a culprit in cases of pancreatitis with unknown etiology. Prompt discontinuation of statins is required in these cases.

A Rare Case of Glioblastoma With Extensive Liver Metastases.

Glioblastoma (GBM), the most common primary brain tumor, is a highly aggressive malignancy for which the median survival is about 13 months, and 5-year survival is well under 5%. These tumors usually occur in the brain and enlarge and infiltrate through white matter, including crossing through the corpus callosum to the opposite cerebral hemisphere. They may spread to distant parts of the central nervous system (CNS) via cerebrospinal fluid pathways. Extraneural metastases from primary brain tumors are quite rare, for 2 probable reasons: because most patients survive less than 2 years, and because of the absence of true lymphatics in the CNS. Typical sites for distant extraneural metastasis of GBM are lungs and pleura, followed by lymph nodes and bones; spread to the liver is exceptional. Most of the reported cases with liver metastases had either single or only a few such metastatic lesions. We report a probably unique case of GBM with extensive liver metastases along with a review of previous cases of liver metastasis from GBM, and we discuss the possible mechanisms of metastasis.

Skewed Inactivation of X Chromosome: A Cause of Hemophilia Manifestation in Carrier Females.

Hemophilia is an X-linked recessive hereditary disorder that classically affects males due to the presence of only one X chromosome in males. Females are usually carriers due to the presence of counterpart X chromosome, but many times manifestations of hemophilia are seen in heterozygous carrier females. This is a result of skewed lionization, in which more normal X chromosomes are converted to bar body, and more abnormal chromosomes remain active in body cells, causing the dominant manifestation of the disease. The severity of manifestations is directly proportional to the level of the clotting factor in the blood. The disease can be severe enough to cause life-threatening bleeding, especially during delivery. Physicians usually reluctant to assume hemophilia in the differential diagnosis of the bleeding disorders in women but manifesting carrier females with hemophilia are not uncommon. Our review of the literature will give an opportunity to understand this issue more precisely as well as will discuss the disease manifestations and its updated management.

A Review of Interstitial Pneumonitis Caused by Elotuzumab Through Case Discussions and Academic Writings.

Patients with relapsed or refractory multiple myeloma have undergone two or three previous therapies are now being treated with a humanized IgG1 monoclonal antibody elotuzumab (HuLuc63) that targets F7 signalling lymphocytic activation molecule F7 (SLAMF7)- a signalling lymphocytic activation molecule. It is combined with dexamethasone and lenalidomide/pomalidomide for therapy. Adverse effects associated with elotuzumab consists of peripheral neuropathy, fever, constitutional symptoms (fatigue, headache, decreased appetite), and infections. A rare side effect of interstitial lung disease has only been observed in a single case. There are two case studies presented below of hypoxic respiratory failure upon this monoclonal antibody treatment both were successfully treated with steroid therapy. This article brings forth the hypothesis that elotuzumab can cause pneumonitis, and discontinuation of elotuzumab along with high-dose corticosteroids helps reverse the pneumonitis.

Spontaneous Bacterial Peritonitis in Cardiogenic Ascites.

The most common cause of ascites is liver cirrhosis. Additional causes such as heart failure, cancer, and pancreatitis among others can also precipitate this abnormality. Spontaneous bacterial peritonitis (SBP) is an infection of ascitic fluid that happens without any evidence of an intra-abdominal surgically-treatable cause. Ascites of cardiac origin can also be complicated by SBP. Here we present a case of a 62-year-old male with extensive cardiac history who presented to our service with ongoing dyspnea and orthopnea. He also had significant abdominal distention and pitting edema. The patient was found to have constrictive pericarditis and was admitted for pericardiectomy. Ascitic fluid was consistent with a transudative process. Lab and imaging did not show evidence of liver or kidney disease. Ascitic fluid was indicative of ascites of cardiac origin. Postoperatively patient developed intermittent fevers initially thought to be due to pericarditis but later found to be due to SBP complicating his recurrent ascites. Such a temporal association of SBP that complicates ascites after pericardiectomy has not been discussed frequently in literature.

Rectus sheath haematoma: a rare masquerader for abdominal pain.

Rectus sheath haematoma is a rare cause of abdominal pain. It can be easily confused for other causes of acute abdomen and may even lead to unnecessary laparotomies. Our patient has the rectus sheath haematoma because of violent coughing and on presentation had no obvious clinical sign pointing to the same. Diagnosis was made by a CT scan of the abdomen, and patient was treated conservatively. Rectus sheath haematomas are usually present on the posterior aspect of the rectus muscles and thus may not be clinically appreciable.