Acute Respiratory Failure.

Respiratory failure is one of the most common reasons for hospitalization and intensive care unit (ICU) admissions, and a diverse range of etiologies can precipitate it. Respiratory failure can result from various mechanisms such as hypoventilation, diffusion impairment, shunting, ventilation-perfusion mismatch, or a combination of those mentioned earlier. Hence, an accurate understanding of different pathophysiologic mechanisms is required for appropriate patient care. Prompt identification and treatment of various respiratory emergencies such as tension pneumothorax, massive hemoptysis, and high-risk pulmonary embolism lead to fewer complications, shorter ICU and hospital stay, and improved survival. This review article entails common respiratory failure pathologies encountered in the ICU and addresses their epidemiology, pathophysiology, clinical presentation, and management.

Acute Liver Failure.

Acute liver failure (ALF) is a rare but life-threatening disease process that can result in rapidly progressive encephalopathy, elevated intracranial pressure, and multiorgan failure. In the United States, the 2 most common causes of ALF in the intensive care unit (ICU) are acetaminophen overdose and hypoxic-ischemic hepatopathy. Less common causes of ALF include alcoholic hepatitis, nonacetaminophen drug-induced liver injury, acute viral hepatitis, Wilson's disease, autoimmune hepatitis, and acute fatty liver of pregnancy. Unfortunately, there are many cases in which the cause of liver failure is indeterminate. ALF is an ICU emergency that requires close monitoring, extensive workup to determine etiology, frequent support of hemodynamic, respiratory, and renal function, administration of targeted therapies depending on the cause, utilization of N-acetylcysteine if appropriate, and consideration for liver transplant in select cases. The primary objective of this article is to define, diagnose, and detail the management of ALF in an ICU setting.

Comparison of universal screening in major lynch-associated tumors: a systematic review of literature.

Lynch syndrome (LS) is associated with an increased lifetime risk of several cancers including colorectal (CRC), endometrial (EC), ovarian (OC), urinary (UT) and sebaceous tumors (ST). The benefit for universal screening in CRC and EC is well known. However, this benefit in other major lynch-associated tumors is unclear. We performed a systematic review of all published articles in the MEDLINE database between 2005 to 2017 to identify studies performing universal screening for LS in unselected CRC, EC, OC, UT and ST. All cases with MSI-H (instability in two or more markers) or missing one or more proteins on IHC testing were considered screening positive. Cases with MLH1 promoter hypermethylation or BRAF mutation positive were considered to have somatic mutations. A total of 3788 articles were identified in MEDLINE yielding 129 study arms from 113 studies. The overall pooled yield of universal LS screening and germline mismatch gene mutation was significantly different across the major LS-associated tumors (Mann Whitney test, p < 0.001). The pooled screening yield was highest in ST [52.5% (355/676), 95% CI 48.74-56.26%] followed by EC [22.65% (1142/5041), 95% CI 21.54-23.86%], CRC [11.9% (5649/47,545), 95% CI 11.61-12.19%], OC [11.29% (320/2833), 95% CI 10.13-12.47%] and UT [11.2% (31/276), 95% CI 7.48-14.92%]. ST also had the highest pooled germline positivity for mismatch repair gene mutation [18.8%, 33/176, 95%CI 13.03-24.57], followed by EC [2.6% (97/3765), 95% CI 2.09-3.11], CRC [1.8% (682/37,220), 95% CI 1.66-1.94%], UT [1.8%(3/164), 95% CI - 0.24-3.83%] and OC [0.83%(25/2983), 95% CI 0.48-1.12%]. LS screening in EC yielded significantly higher somatic mutations compared to CRC [pooled percentage 16.94% [(538/3176), 95%CI 15.60-18.20%] vs. 5.23% [(1639/26,152), 95% CI 4.93-5.47%], Mann Whitney test, p < 0.0001. Universal LS testing should be routinely performed in OC, UT and STs in addition to CRC and EC. Our findings also support consideration for IHC and somatic mutation testing before germline testing in EC due to higher prevalence of somatic mutations as well as germline testing in all patients with ST. Our results have implications for future design of LS screening programs and further studies are needed to assess the cost effectiveness and burden on genetic counselling services with expanded universal testing for LS.

Coincidence or connection? A patient with concurrent Lane Hamilton Syndrome and idiopathic membranous nephropathy.

Lane Hamilton Syndrome is the rare association of idiopathic pulmonary hemosiderosis and Celiac Disease. The definitive pathophysiologic link is unknown, but the syndrome has been described as co-occurring along with other diseases. We describe the first reported case of Lane Hamilton Syndrome and idiopathic membranous nephropathy. We also hypothesize the possibility of an immune-mediated connection between the pathologies and propose a potential link of the phospholipase A2 receptor.

Worldwide variation in lynch syndrome screening: case for universal screening in low colorectal cancer prevalence areas.

To perform a systematic assessment of universal Lynch syndrome (LS) screening yield in colorectal cancer (CRC) patients around the world. Universal screening for LS is recommended in all CRC patients. However, the variation in yield of LS screening in the setting of significant global variation in CRC prevalence is unknown. A systematic review of articles in the MEDLINE database was performed to identify studies performing universal screening for LS. All cases with microsatellite instability (MSI-H) or missing one or more proteins on immunohistochemistry (IHC) were considered screening positive. The overall pooled yield of universal LS screening in 97 study arms from 89 identified studies was 11.9% (5649/47545) and the overall pooled percentage of confirmed LS patients was 1.8% (682/37220). LS screening positivity varied significantly based on geographic region (Kruskal Wallis test, p < 0.001) and reported 5-year CRC prevalence in the country (Fisher's exact, p < 0.001). Significant inverse correlation was found between LS screening positivity and 5-year CRC prevalence (Pearson correlation, r = - 0.56, p < 0.001). The overall yield of LS screening was 15.00% (382/2553) and rate of confirmed LS was 7.7% (113/1475) in LS screening done in patients ≤ 50 years (16 studies). There is significant geographic variation in LS screening positivity with higher yield in countries with lower prevalence of CRC. Our results highlight the importance of universal LS screening in younger patients and low CRC prevalence countries.

Comorbidities Associated With Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease or COPD is characterized by airflow obstruction, causing respiratory symptoms. There are treatments available for COPD; however, COPD has significant extrapulmonary effects, including well-recognized ones as cardiovascular disease and often underdiagnosed ones as osteoporosis. It is imperative to be aware of these comorbidities to optimize COPD patient care.

Developing a Multidisciplinary Approach to the COPD Care Pathway.

Chronic obstructive pulmonary disease (COPD) is characterized as a predominately preventable and treatable inflammatory lung disease caused by progressive obstructed airflow from the lungs. In the United States and worldwide, it is becoming a major cause in hospital admissions as well as an increase in morbidity and mortality. The rising total cost of care for COPD is concerning for all health care industries. The disease has significant impact on the patient's quality of life and psychological well-being. A worldwide initiative is underway in developing a care model that is multifactorial through continuous monitoring of patients to manage and control symptoms, achieve medication adherence, and provide socioeconomic resources. The primary aim of this study was to prevent exacerbations, hospital admissions, and readmissions. Various models have shown positive results; however, the significant financial investment is the major barrier to success. Recently, one health system in the United States was able to improve care, decrease readmissions, and reduce total cost of care by investing in a multidisciplinary team of specialists. In the utilization of the care model, the primary endpoint will conclude that COPD is financially and socioeconomically manageable.

COVID-19: Epidemiology, Pathophysiology, Transmission, Symptoms.

COVID-19 is caused by the coronavirus known as SARS-CoV2. This virus may lead to asymptomatic cases, mild illness, or acute respiratory distress syndrome. Here we describe the epidemiology, pathophysiology, transmission, and symptoms of the virus.

Endoscopic suturing for management of peptic ulcer-related upper gastrointestinal bleeding: a preliminary experience.

Background and study aims Acute non-variceal upper gastrointestinal bleeding (UGIB) due to peptic ulcer disease (PUD) remains a common and challenging emergency managed by gastroenterologists. The proper role of endoscopic suturing on the management of PUD-related UGIB is unknown. Patients and methods This is an international case series of patients who underwent endoscopic suturing for bleeding PUD. Primary outcome was rate of immediate hemostasis and rate of early rebleeding (within 72 hours). Secondary outcomes included technical success, delayed rebleeding (> 72 hours), and rate of adverse events (AEs). Results Ten patients (mean age 66.7 years, 30 % female) were included in this study. Nine (90 %) had prior failed endoscopy hemostasis with an average of 1.4 ±â€Š0.7 (range 1 - 3) prior endoscopic sessions. Forrest classification was Ib in 5 (50 %), IIa in 3 (30 %), IIb in 1(10 %), and IIc in 1 (10 %). Mean suturing time was 13.4 ±â€Š5.6 (range 3.5 to 20) minutes. Technical success was 100 %. Rate of immediate hemostasis was 100 % and rate of early rebleeding was 0 %. Mean number of sutures was 1.5 (range, 1 - 4). No AEs were observed. Delayed recurrent bleeding was not observed in any cases after a median of 11 months (range 2 - 56), after endoscopic suturing. Conclusions Oversewing of a bleeding or high-risk ulcer using endoscopic suturing appears to be a safe and effective method for achieving endoscopic hemostasis. It may be considered as rescue endoscopic therapy when primary endoscopic hemostasis fails to control the bleeding or when hemorrhage recurs after successful control of bleeding.

Fully-covered metal stents with endoscopic suturing vs. partially-covered metal stents for benign upper gastrointestinal diseases: a comparative study.

BACKGROUND AND STUDY AIMS: Self-expandable metallic stents (SEMS) have been increasingly used in benign conditions (e. g. strictures, fistulas, leaks, and perforations). Fully covered SEMS (FSEMS) were introduced to avoid undesirable consequences of partially covered SEMS (PSEMS), but come with higher risk of stent migration. Endoscopic suturing (ES) for stent fixation has been shown to reduce migration of FSEMS. Our aim was to compare the outcomes of FSEMS with ES (FS/ES) versus PSEMS in patients with benign upper gastrointestinal conditions. PATIENTS AND METHODS: We retrospectively identified all patients who underwent stent placement for benign gastrointestinal conditions at seven US tertiary-care centers. Patients were divided into two groups: FSEMS with ES (FS/ES group) and PSEMS (PSEMS group). Clinical outcomes between the two groups were compared. RESULTS: A total of 74 (FS/ES 46, PSEMS 28) patients were included. On multivariable analysis, there was no significant difference in rate of stent migration between FS/ES (43 %) and PSEMS (15 %) (adjusted odds ratio 0.56; 95 % CI 0.15 - 2.00). Clinical success was similar [68 % vs. 64 %; P  = 0.81]. Rate of adverse events (AEs) was higher in PSEMS group [13 (46 %) vs. 10 (21 %); P  = 0.03). Difficult stent removal was higher in the PSEMS group (n = 5;17 %) vs. 0 % in the FS/ES group; P  = 0.005. CONCLUSIONS: The proportion of stent migration of FS/ES and PSEMS are similar. Rates of other stent-related AEs were higher in the PSEMS group. PSEMS was associated with tissue ingrowth or overgrowth leading to difficult stent removal, and secondary stricture formation. Thus, FSEMS with ES for stent fixation may be the preferred modality over PSEMS for the treatment of benign upper gastrointestinal conditions.

Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the Breast.

BACKGROUND: Invasive lobular carcinoma (ILC) comprises around 10 - 15% of invasive breast cancers. Few prior studies have demonstrated a unique pattern of metastases between ILC and the more common invasive ductal carcinoma (IDC). To our knowledge, such data is limited to first sites of distant recurrence. We aimed to perform a comparison of the metastatic pattern of ILC and IDC at first distant recurrence as well as over the entire course of metastatic disease. METHODS: We used a prospectively collated database of patients with metastatic breast cancer. Breast cancer recurrence or metastases were classified into various sites and a descriptive analysis was performed. RESULTS: Among 761 patients, 88 (11.6%) were diagnosed with ILC and 673 (88.4%) with IDC. Patients with ILC showed more frequent metastases to the bone (56.8 vs. 37.7%, p = 0.001) and gastrointestinal (GI) tract (5.7 vs. 0.3%, p < 0.001) as first site of distant recurrence, and less to organs such as lung (5.7 vs. 24.2%, p < 0.001) and liver (4.6 vs. 11.4%, p = 0.049). Over the entire course of metastatic disease, more patients with ILC had ovarian (5.7 vs. 2.1%, p = 0.042) and GI tract metastases (8.0 vs. 0.6%, p < 0.001), also demonstrating reduced tendency to metastasize to the liver (20.5 vs. 49.0%, p < 0.001) and lung (23.9 vs. 51.9%, p < 0.001). All associations but bone held after sensitivity analysis on hormonal status. Although patients presenting with ILC were noted to have more advanced stage at presentation, recurrence-free survival in these patients was increased (4.8 years vs. 3.2 years, p = 0.017). However, overall survival was not (2.5 vs. 2.0 years, p = 0.75). CONCLUSION: After accounting for hormone receptor status, patients with IDC had greater lung/pleura and liver involvement, while patients with ILC had a greater propensity to develop ovarian and GI metastases both at first site and overall. Clinicians can use this information to provide more directed screening for metastases; it also adds to the argument that these two variants of breast cancer should be managed as unique diseases.

Prevalence and determinants of end-of-life chemotherapy use in patients with metastatic breast cancer.

Cessation of chemotherapy in the last few weeks of life could be an important quality-of-care benchmark. Proportion of metastatic breast cancer patients who receive end-of-life chemotherapy is not well described. We aimed to determine the prevalence and determinants of end-of-life chemotherapy use in patients with metastatic breast cancer. A retrospective cohort study using a prospectively collated database of patients with metastatic breast cancer who died between January 1, 2010, and September 30, 2014, was conducted. End-of-life chemotherapy (EOLC) use was defined as receipt of chemotherapy within 2 weeks of death (EOLC2) and receipt of chemotherapy within 4 weeks of death (EOLC4). Patients who did not receive any chemotherapy in the last 4 weeks before death were categorized as non-EOLC. We identified 274 patients with metastatic breast cancer, of whom 28 received EOLC2 (10.2%) and 62 received EOLC4 (22.6%). In comparison with non-EOLC, patients receiving EOLC4 were younger and had greater disease burden. Patients in EOLC4 group received more number of lines of chemotherapy. In a multivariable analysis, younger age at metastatic disease and greater number of metastatic organ systems involved were predictors of end-of-life chemotherapy use. Prevalence of the use of end-of-life chemotherapy in our cohort was higher than previously described. More end-of-life chemotherapy was used in younger women, and those with greater disease burden. Earlier initiation of end-of-life discussions may be targeted to such patients.

Hyperkalemia from Dietary Supplements.

Hyperkalemia is a common electrolyte problem in patients with chronic kidney disease. It is typically caused by medications in patients with poor kidney function. Patients with comorbodities such as heart failure and diabetes are predisposed to electrolyte problems. Salt substitutes and dietary supplements are uncommon causes of hyperkalemia, but we propose that they are under-recognized and underdiagnosed causes in patients with chronic kidney disease. Our case report and literature review illustrates that a careful dietary history is essential in patients presenting with electrolyte disorders, especially hyperkalemia.

Leukapheresis in patients newly diagnosed with acute myeloid leukemia.

Hyperleukocytosis is present in 5 to 20 percent of patients with newly diagnosed acute myeloid leukemia (AML). The management of hyperleukocytosis, when symptoms of leukostasis occur, includes intensive supportive care and interventions for rapid cytoreduction. Leukapheresis is a rapid and effective means of cytoreduction and has been used in AML patients. In the current study, we evaluated the outcomes of 68 newly diagnosed AML patients that underwent leukapheresis and the effects of leukapheresis on various laboratory parameters. A total of 127 leukapheresis cycles were performed. The median number of leukapheresis cycles was 2 (range, 1-8). The overall survival for all patients was 4.2 months (95% CI 1.2-9.7 months). The median overall survival for patients who achieved complete remission after induction chemotherapy was significantly higher (19.1 months [95% CI 12.1-41.8 months]) than patients that did not achieve complete remission (0.46 months [95% CI 0.33-0.99 months]). Stepwise logistic regression demonstrated that elevated number of peripheral blasts, low platelet count and elevated bilirubin at AML diagnosis were predictive of death within a week. Leukapheresis was effective in reducing the peripheral blood leukocytes and leukemia blasts and was a safe procedure with regard to organ function, coagulation parameters, red blood cells and platelet count. The high initial response rates in newly diagnosed AML patients fit to receive intensive chemotherapy suggest that leukapheresis could be beneficial in reducing the complications associated with hyperleukocytosis until systemic intensive chemotherapy commences.