Ectopic Cushing's syndrome in a patient with metastatic Merkel cell carcinoma: A case report.

BACKGROUND: Ectopic Cushing syndrome (ECS) is a rare condition commonly associated with neuroendocrine tumors (NET), mainly bronchial carcinoids. The association of paraneoplastic syndrome with Merkle cell carcinoma (MCC) is limited to individual case reports. CASE SUMMARY: In this article we report an unusual and striking presentation of ECS in a patient with known metastatic MCC. An elderly patient presented with new onset severe hypertension, hyperglycemia and hypokalemia, muscle wasting, and peripheral edema. A diagnosis of adrenocorticotropic hormone dependent, non-pituitary, Cushing syndrome was established. Medical therapy inhibiting adrenal function was promptly started but unfortunately the patient survived only a few days after diagnosis. CONCLUSION: The occurrence of an aggressive form of ECS in patients with NET should be recognized as an ominous event. To our knowledge, the association of this complication in a patient with MCC had not been reported.

Associations between different measures of intra-operative tachycardia during noncardiac surgery and adverse postoperative outcomes: A retrospective cohort analysis.

BACKGROUND: Intra-operative tachycardia during noncardiac surgery has been associated with adverse postoperative outcomes. However, harm thresholds for tachycardia have not been uniformly defined. The definition of intra-operative tachycardia that best correlates with adverse postoperative outcomes remains unclear. OBJECTIVE: We aimed to identify the definition of intra-operative tachycardia during noncardiac surgery that is associated with the best predictive ability for adverse postoperative outcomes. DESIGN: A single-centre retrospective cohort analysis. SETTING: Secondary care hospital, Afula, Israel. PATIENTS AND METHODS: Adults who underwent elective or nonelective noncardiac surgery during 2015 to 2019. Five intra-operative heart rate (HR) cut-off values and durations were applied with penalised logistic regression modelling for the outcome measures. MAIN OUTCOME MEASURES: The primary outcome was all-cause 30-day mortality; the secondary outcome was myocardial ischaemia or infarction (MI) within 30 days after noncardiac surgery. RESULTS: The derivation and validation datasets included 6490 and 4553 patients, respectively. Altogether, all-cause 30-day mortality and MI rates averaged 2.1% and 3.2%, respectively. Only two definitions of intra-operative tachycardia were significantly associated with the outcome measures: HR ≥ 100 bpm for ≥ 30 min and HR ≥ 120 bpm for ≥ 5 min. The C-statistics of the base models without tachycardia exposure for all-cause 30-day mortality and MI were 0.75 (95% confidence interval, CI, 0.74 to 0.78) and 0.73 (95% CI, 0.72 to 0.76), respectively. The addition of intra-operative tachycardia exposure to the base models significantly improved their predictive performance. The highest area under the curve (AUC) was achieved when tachycardia was defined as an intra-operative HR ≥ 100 bpm for at least 30 min: AUC 0.81 (95% CI, 0.80 to 0.84) and AUC 0.80 (95% CI, 0.79 to 0.82) for all-cause 30-day mortality and MI, respectively. CONCLUSION: Intra-operative tachycardia, defined as an intra-operative HR ≥ 100 bpm for at least 30 min, was associated with the highest predictive power for adverse postoperative outcomes.

Candida Bloodstream Infection, a Dire Complication in Hospitalized COVID-19 Patients: Three Cases from a Single Center in Northern Israel.

BACKGROUND: Patients with severe coronavirus disease-2019 (COVID-19) are susceptible to superimposed infections. OBJECTIVES: To describe COVID-19 patients who presented with complications due to Candida bloodstream co-infection (candidemia) and their outcome in a single center in northern Israel (Emek Medical Center) during the second outbreak of COVID-19 in Israel (15 June 2020 to 20 September 2020). METHODS: A retrospective study of COVID-19 patients presenting with candidemia was conducted, including clinical and laboratory data. The incidence of candidemia among hospitalized COVID-19 patients was compared to a historical cohort of non-COVID-19 controls. RESULTS: Three COVID-19 patients complicated with candidemia were documented. All three patients died shortly after the detection of candidemia. Three different Candida sp. were isolated from the blood cultures: C. albicans, C. parapsilosis, and C. glabrata. The incidence of candidemia among COVID-19 patients was 0.679 episodes per 1000 hospital days. CONCLUSIONS: Our small sample suggests a much higher incidence of candidemia among COVID-19 patients compared to a historical cohort of non-COVID-19 controls. All clinicians treating COVID-19 patients in GICU should be aware of this complication.

Is fasting still necessary prior to contrast-enhanced computed tomography? A randomized clinical study.

OBJECTIVES: There is very limited evidence to support the common practice of preparative fasting prior to contrast-enhanced computerized tomography (CT). This study examined the effect of withholding fasting orders, prior to contrast-enhanced CT, on the incidence of aspiration pneumonitis and adverse gastrointestinal symptoms. METHODS: This randomized controlled trial enrolled hospitalized patients referred for non-emergency, contrast-enhanced CT scan to either at least 4 h of fasting or to an unrestricted consumption of liquids and solids up to the time of CT. The primary outcome was incidence of aspiration pneumonitis and the secondary outcomes were rates of adverse gastrointestinal symptoms (nausea and/or vomiting). RESULTS: After excluding participants with incomplete follow-up, a total of 1080 participants were assigned to the fasting group and 1011 were assigned to the non-fasting group. Aspiration pneumonitis was not identified in either group. The mean time of fasting in the fasting group was 8.4 ± 1.6 h. Rates of nausea and vomiting were not statistically different between the fasting group compared with the non-fasting group, 6.6% vs. 7.6% (p = 0.37) and 2.6% vs. 3.0% (p = 0.58), respectively. A subgroup analysis of patients who were required to drink oral contrast agent (n = 1257) showed that rates of nausea and vomiting were not statistically different between the fasting and non-fasting groups, 6.8% vs. 8.0% (p = 0.42) and 2.6% vs. 3.6% (p = 0.3), respectively. CONCLUSIONS: Withholding fasting orders prior to contrast-enhanced CT was not associated with a greater risk of aspiration pneumonitis or a significant increase in rates of adverse gastrointestinal symptoms. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03533348 KEY POINTS: • Is fasting necessary prior to contrast-enhanced computed tomography (CT)? • In this randomized clinical study including 2091 participants referred to non-emergency contrast-enhanced CT scan, withholding preparative fasting was not associated with a greater risk of aspiration pneumonitis or clinically significant increase in rates of adverse gastrointestinal symptoms. • Eating and drinking prior to contrast-enhanced CT can be allowed and are not associated with an increased risk of aspiration pneumonitis.

Method for Specific Identification of the Emerging Zoonotic Pathogen Vibrio vulnificus Lineage 3 (Formerly Biotype 3).

Vibrio vulnificus is a zoonotic pathogen that is spreading worldwide due to global warming. Lineage 3 (L3; formerly biotype 3) includes the strains of the species with the unique ability to cause fish farm-linked outbreaks of septicemia. The L3 strains emerged recently and are particularly virulent and difficult to identify. Here, we describe a newly developed PCR method based on a comparative genomic study useful for both rapid identification and epidemiological studies of this interesting emerging group. The comparative genomic analysis also revealed the presence of a genetic duplication in the L3 strains that could be related to the unique ability of this lineage to produce septicemia outbreaks.

Phylogeography of the marine pathogen, Vibrio vulnificus, revealed the ancestral scenarios of its evolution.

Vibrio vulnificus is the leading cause of seafood-associated deaths worldwide. Despite the growing knowledge about the population structure of V. vulnificus, the evolutionary history and the ancestral relationships of strains isolated from various regions around the world have not been determined. Using the largest collection of sequence and isolate data of V. vulnificus to date, we applied ancestral character reconstruction to study the phylogeography of V. vulnificus. Multilocus sequence typing data from 10 housekeeping genes were used for the inference of ancestral states and reconstruction of the evolutionary history. The findings showed that the common ancestor of all V. vulnificus populations originated from East Asia, and later evolved into two main clusters that spread with time and eventually evolved into distinct populations in different parts of the world. While we found no meaningful insights concerning the evolution of V. vulnificus populations in the Middle East; however, we were able to reconstruct the ancestral scenarios of its evolution in East Asia, North America, and Western Europe.

The utility of adding symptoms and signs to the management of injury-related pain.

OBJECTIVE: Improved pain assessment and management in the emergency department (ED) is warranted. We aimed to determine the impact on pain management, of adding symptoms and signs to pain assessment. PATIENTS AND METHODS: A single center before-and-after study was conducted, supplemented by an interrupted time series analysis. The intervention included the addition of clinical presentation (CP) of the injury and facial expression (FE) of the patient to pain assessment scales of patients with soft tissue injures. Pain intensity was categorized as: mild, moderate, and severe. We compared types of pain relief medications, use of strong opioids, and pain relief efficacy between pre and post intervention phases. RESULTS: Before-and-after analysis revealed a significant reduction in the use of strong opioids. The adjusted relative ratio for the use of strong opioids in the post intervention phase was 0.63 (95% CI: 0.48-0.82). This reduction was mostly driven by less use of strong opioids in patients reporting severe pain (from 17.3%-7.9%) (P < 0.0001). A larger proportion of patients in the post intervention phase than in the pre intervention phase received weak opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) (27.4% vs 19.1%, P = 0.002), and a larger proportion did not receive any pain relief medication (19.8% vs 10.5%, p < 0.0001). The use of strong opioids increased with higher levels of FE and CP. Among patients with mild injury and reporting severe pain, the odds of receiving a strong opioid was nearly 9 times (OR = 8.9, 95% CI: 4.0-19.6) higher among those who were with an unrelaxed FE and showed pain behavior than those with relaxed FE. Interrupted time-series analysis showed that the mean ΔVAS (VAS score at entry minus VAS score at discharge) in the post intervention phase compared with the pre intervention phase was not statistically significant (P = 0.073). The use of strong opioids in the post intervention phase was significantly reduced (P = 0.017). CONCLUSION: Adding symptoms and signs to pain assessment of patients admitted with soft tissue injuries decreased the use of strong opioids, without affecting pain relief efficacy.

Trends in admission serum albumin and mortality in patients with hospital readmission.

AIMS: To determine the relationship between trends in admission serum albumin and long-term mortality in medical patients with hospital readmission. MATERIALS AND METHODS: We used a cohort of patients admitted to five departments of internal medicine during 3 years. Survival analysis was performed based on mean admission serum albumin levels and trends in albumin values from recurrent admissions. RESULTS: A total of 5396 patients had 16 640 admissions (readmission cohort), another 9422 patients were admitted only once (single admission cohort). Readmitted patients with low mean albumin were older, predominantly females and had higher comorbidity index than patients with normal mean albumin. The 6-month all-cause mortality rate of the normal and low mean albumin groups was 5.2% and 24.2%, respectively (P < 0.001). Survival analysis showed that patients with persistently normal albumin levels had the highest survival rates at 6 months (97.7%), compared with patients who had hypoalbuminemia at index admission but normalised their albumin levels in subsequent admissions (92%), patients with declining albumin trends (85.6%) and patients with persistently low albumin levels (68.9%) (P < 0.0001). CONCLUSIONS: Serum albumin is strongly associated with long-term mortality in readmitted medical patients. Persistent hypoalbuminemia during recurrent admissions is associated with increased risk of long-term mortality.

Predictive modeling of inpatient mortality in departments of internal medicine.

Despite overwhelming data on predictors of inpatient mortality, it is unclear which variables are the most instructive in predicting mortality of patients in departments of internal medicine. This study aims to identify the most informative predictors of inpatient mortality, and builds a prediction model on an individual level, given a constellation of patient characteristics. We use a penalized method for developing the prediction model by applying the least-absolute-shrinkage and selection-operator regression. We utilize a cohort of adult patients admitted to any of 5 departments of internal medicine during 3.5 years. We integrated data from electronic health records that included clinical, epidemiological, administrative, and laboratory variables. The prediction model was evaluated using the validation sample. Of 10,788 patients hospitalized during the study period, 874 (8.1%) died during admission. We find that the strongest predictors of inpatient mortality are prior admission within 3 months, malignant morbidity, serum creatinine levels, and hypoalbuminemia at hospital admission, and an admitting diagnosis of sepsis, pneumonia, malignant neoplastic disease, or cerebrovascular disease. The C-statistic of the risk prediction model is 89.4% (95% CI 88.4-90.4%). The predictive performance of this model is better than a multivariate stepwise logistic regression model. By utilizing the prediction model, the AUC for the independent (validation) data set is 85.7% (95% CI 84.1-87.3%). Using penalized regression, this prediction model identifies the most informative predictors of inpatient mortality. The model illustrates the potential value and feasibility of a tool that can aid physicians in decision-making.

Twenty Year Trends of Survival after In-Hospital Cardiac Arrest.

BACKGROUND: In 2006, the Israeli Ministry of Health distributed guidelines for improving cardiopulmonary resuscitation (CPR) knowledge among hospital staff. The impact of these guidelines on survival after in-hospital cardiac arrest (IHCA) is unclear. OBJECTIVES: To compare rates of incidence and survival to discharge after IHCA, preceding and subsequent to issuance of the guidelines: 1995-2005 and 2006-2015. METHODS: Data were retrieved from the computerized records of patients who had an IHCA and underwent CPR. In addition, we retrieved data available from the hospital's resuscitation committee that included number, type, methods of training in CPR refresher courses, type and number of audits carried out during the past 10 years, and type of CPR quality assessments. RESULTS: From 1995 to 2015, IHCA incidence increased from 0.7 to 1.7 per 1000 admissions (P < 0.001), while survival rate did not increase (P = 0.37). Survival for shockable rhythms increased from 15.4 to 30.2% (P = 0.05) between the two time periods. The ratio of non-shockable to shockable rhythms increased from 2.4 to 4.6 (P = 0.01) between the two time periods. CONCLUSIONS: Overall IHCA survival did not improve following the issuance of guidelines requiring CPR refresher courses, although survival improved for patients with initial shockable dysrhythmia. A decrease of events with initial shockable dysrhythmia, an increase with acute renal failure, and a decrease occurring in intensive care units contributed to understanding the findings. We found that CPR refresher courses were helpful, although an objective measure of their effectiveness is lacking.

Fatal delayed haemolytic transfusion reaction in a patient without previous transfusions but with an obstetric history of 13 pregnancies.

Delayed haemolytic transfusion reaction is a rare, life-threatening complication of blood transfusion that has been typically described among patients with sickle cell disease (SCD) due to alloimmunisation induced by their exposure to red blood cell antigens through recurrent transfusions. We report the case of a patient who suffered from fatal delayed haemolytic transfusion reaction (DHTR) occurring 1 week after blood transfusion. Indirect antiglobulin testing confirmed the presence of anti-Kell antibodies that were absent in the pretransfusion sample. The patient did not receive blood transfusions in the past, but her obstetric history was remarkable for 13 pregnancies. Although DHTR occurs more commonly among patients with SCD, this type of reaction can occur in any patient who is able to mount an immune response. We would to like to draw the attention of physicians to this rare and potentially lethal complication of blood transfusion, especially in grand multiparous women.

Rapidly Progressive Bioprosthetic Aortic Valve Stenosis Due to Bartonella Species Endocarditis.

Rapid progression of valvular stenosis in the setting of infective endocarditis is extremely rare. Here we describe a patient with Bartonella endocarditis on a bioprosthetic aortic valve that caused rapidly progressive aortic stenosis without regurgitation. At operation the bioprosthetic valve was severely fibrotic and calcified, with markedly thickened and distorted leaflets and circular partial detachment from the aortic ring. The patient underwent aortic root replacement with aortic bioprosthesis and aortic grafting with reimplantation of the coronary ostia.

The derivation and validation of a simple model for predicting in-hospital mortality of acutely admitted patients to internal medicine wards.

Limited information is available about clinical predictors of in-hospital mortality in acute unselected medical admissions. Such information could assist medical decision-making.To develop a clinical model for predicting in-hospital mortality in unselected acute medical admissions and to test the impact of secondary conditions on hospital mortality.This is an analysis of the medical records of patients admitted to internal medicine wards at one university-affiliated hospital. Data obtained from the years 2013 to 2014 were used as a derivation dataset for creating a prediction model, while data from 2015 was used as a validation dataset to test the performance of the model. For each admission, a set of clinical and epidemiological variables was obtained. The main diagnosis at hospitalization was recorded, and all additional or secondary conditions that coexisted at hospital admission or that developed during hospital stay were considered secondary conditions.The derivation and validation datasets included 7268 and 7843 patients, respectively. The in-hospital mortality rate averaged 7.2%. The following variables entered the final model; age, body mass index, mean arterial pressure on admission, prior admission within 3 months, background morbidity of heart failure and active malignancy, and chronic use of statins and antiplatelet agents. The c-statistic (ROC-AUC) of the prediction model was 80.5% without adjustment for main or secondary conditions, 84.5%, with adjustment for the main diagnosis, and 89.5% with adjustment for the main diagnosis and secondary conditions. The accuracy of the predictive model reached 81% on the validation dataset.A prediction model based on clinical data with adjustment for secondary conditions exhibited a high degree of prediction accuracy. We provide a proof of concept that there is an added value for incorporating secondary conditions while predicting probabilities of in-hospital mortality. Further improvement of the model performance and validation in other cohorts are needed to aid hospitalists in predicting health outcomes.

Septic Thrombophlebitis with Persistent Methicillin-Resistant Staphylococcus Aureus Bacteremia and de Novo Resistance to Vancomycin and Daptomycin.

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with significant risk of mortality, especially when it occurs while on appropriate antimicrobial therapy. We herein describe an unusual case of a patient with prosthetic aortic tissue valve, who suffered from central venous catheter related MRSA bacteremia with septic thrombus formation in the superior vena cava. MRSA bacteremia persisted despite removal of the catheter and appropriate antimicrobial therapy including vancomycin, rifampin, and daptomycin. Subsequently, the MRSA strain exhibited de novo resistance to vancomycin, rifampin and daptomycin. Eventually, salvage combination therapy with high dose daptomycin and trimethoprim-sulfamethoxazole was successful and achieved clearance of MRSA bacteremia. The case illustrates the growing complexity of treating MRSA infections.

Outcome of mechanically ventilated patients initially denied admission to an intensive care unit and subsequently admitted.

The outcome of mechanically ventilated patients initially denied admission to an intensive care unit (ICU) and subsequently admitted is unclear. We compared outcomes of patients denied ICU admission and subsequently admitted, to those of patients admitted to the ICU and to patients refused ICU admission. The medical records of all the patients who were subjected to mechanical ventilation for at least 24h over a 4year period (2010-2014) were reviewed. Of 707 patients (757 admissions), 124 (18%) were initially denied ICU admission and subsequently admitted. Multivariate stepwise logistic regression analysis showed significant association with death of: age, length of stay, nursing home residency, duration of mechanical ventilation, previous admission with mechanical ventilation, cause for mechanical ventilation, rate of failed extubations, associated morbidity (previous cerebrovascular accident, dementia, chronic renal failure), and occurrence of nosocomial bacteremia. The odds for death among patients denied ICU admission and subsequently transferred to the ICU compared to patients admitted directly to the ICU was 3.6 (95% CI: 1.9-6.7) (P<0.0001). The odds for death among patients refused ICU admission compared to those who were initially denied and subsequently admitted were not statistically significant (OR=1.7, 95% CI: 0.8-3.8). In conclusion, patients denied ICU admission and subsequently admitted face a considerable risk of morbidity and mortality. Their odds of death are nearly three times those admitted directly to the ICU. Late admission to the ICU does not appear to provide benefit compared to patients who remain in general medicine wards.

Draft Genome Sequences of Streptococcus pneumoniae with High-Level Resistance to Respiratory Fluoroquinolones.

Streptococcus pneumoniaeis the leading cause of community-acquired pneumonia. Levofloxacin is a fluoroquinolone used for treatment of severe community-acquired pneumonia. Here, we describe the draft genome sequences ofS. pneumoniaewith emerging resistance to levofloxacin, resulting in failure of treatment of pneumococcal pneumonia.