Primary Adrenal Insufficiency After COVID-19 Infection.

BACKGROUND/OBJECTIVE: The multisystemic effects of COVID-19 are becoming evident. In the adrenal gland, adrenal hemorrhage and infarction after COVID-19 infection have been reported. Our objective is to present a case of autoimmune adrenal insufficiency diagnosed after COVID-19 infection, without the evidence of a hemorrhage or an infarction. CASE REPORT: A 64-year-old woman with hypothyroidism and type 2 diabetes presented with a 1-week history of abdominal pain, nausea, and vomiting. She had experienced asymptomatic COVID-19 infection 5 months prior and reported an unintentional 30-lb weight loss. The home medications included enalapril, atorvastatin, and levothyroxine. A physical examination was notable for hypotension, epigastric tenderness, and mucocutaneous hyperpigmentation. Laboratory tests revealed a serum sodium level of 117 mmol/L (range, <20 mmol/L), thyroid-stimulating hormone level of 0.33 µIU/mL (range, 0.35-4.00 µIU/mL), free thyroxine level of 1.4 ng/dL (range, 0.6-1.7 ng/dL), serum osmoles of 253 mOsm/kg (range, 279-300 mOsm/kg), urine osmoles of 324 mOsm/kg (range, 300-900 mOsm/kg), and urine sodium level of 104 mmol/L. The morning cortisol level was 2.6 µg/dL (reference [ref], >18 µg/dL). This was followed by a high-dose, 250-µg adrenocorticotropic hormone (ACTH) stimulation test, which revealed that the cortisol level was 2.3, 2.9, and 2.6 µg/dL (ref, >18 µg/dL) at baseline, 30 minutes, and 60 minutes, respectively. The ACTH level was 1944 pg/mL (range, 7.2-63.3 pg/mL), the aldosterone level was <3.0 ng/dL (range, 4.0-31.0 ng/dL), and anti-21-hydroxylase antibody was present (ref, negative). A computed tomography scan of the adrenals was unremarkable. Hypotension and hyponatremia resolved after initiation of intravenous hydrocortisone, and she was discharged on hydrocortisone and fludrocortisone. DISCUSSION: The patient's symptoms, elevated ACTH level, low cortisol level, and presence of 21-hydroxylase antibodies were consistent with Addison disease. COVID-19 might have contributed to rapid, clinically relevant disease progression after the infection. CONCLUSION: The development of autoimmune Addison disease in the patient might be related to the prior COVID-19 infection.

CAUTION ADVISED USING COMBINATION KETOCONAZOLE AND PD-1 INHIBITORS.

OBJECTIVE: Immune checkpoint inhibitors are approved to treat multiple cancers. We report life-threatening hepatic failure in 2 consecutive patients with Cushing syndrome that were treated with ketoconazole (KTZ) in combination with 2 different programmed cell death protein 1 (PD-1) inhibitors, Nivolumab and Pembrolizumab. METHODS: The first patient suffered from corticotroph pituitary carcinoma and the second from metastatic adrenal cortical carcinoma. They were both treated with KTZ for tumor-associated hypercortisolism. RESULTS: Hepatic function was normal on KTZ prior to initiation of PD-1 inhibitors, after which they rapidly developed severe hepatic dysfunction. In both cases, liver biopsy was consistent with drug-induced hepatic injury. Liver function fully recovered on discontinuing KTZ and the PD-1 inhibitors along with methylprednisone therapy. CONCLUSION: Antifungal azole therapy is commonly used in oncology patients who may be co-treated with PD-1 inhibitors. Although the specific combination of KTZ and PD-1 inhibitors to treat Cushing syndrome may be relatively uncommon, we recommend careful monitoring of hepatic function using a combination PD-1 inhibitors and azole antifungal agents, especially KTZ, due to the potential of life-threatening hepatic failure.

Anesthetic management of pediatric patients diagnosed with X-linked adrenoleukodystrophy: A single-center experience.

BACKGROUND: X-linked adrenoleukodystrophy is a progressive demyelinating disease that primarily affects males with an incidence of 1:20 000-30 000. The disease has a wide spectrum of phenotypic expression and may include adrenal insufficiency, cerebral X-linked adrenoleukodystrophy and adrenomyeloneuropathy. The condition has implications for the administration of anesthesia and reports of anesthetic management in those patients are limited at this point. AIM: To review the perioperative care, complications and outcomes of patients diagnosed with X-linked adrenoleukodystrophy at the University of Minnesota Masonic Children's Hospital. METHOD: After obtaining IRB approval, we performed a retrospective chart review of pediatric patients diagnosed with X-linked adrenoleukodystrophy who underwent either surgery or diagnostic/therapeutic procedures that included anesthesia services between January 2014 and December 2016. Data included demographics, American Society of Anesthesiologists classification, preoperative diagnosis, history of hematopoietic stem cell transplant, anesthetic approaches, airway management, medications used, intra- and postoperative complications, and patient disposition. RESULTS: We identified 38 patients who had a total of 166 anesthetic encounters. The majority of patients underwent procedures in the sedation unit (75.9%) and received a total intravenous anesthetic with spontaneous ventilation via a natural airway (86.1%). Preoperative adrenal insufficiency was documented in 87.3% of the encounters. Stress-dose steroids were administered in 70.5% of the performed anesthetics. A variety of anesthetic agents were successfully used including sevoflurane, isoflurane, propofol, midazolam, ketamine, and dexmedetomidine. There were few perioperative complications noted (6.6%) and the majority were of low severity. No anesthesia-related mortality was observed. CONCLUSIONS: With the availability of skilled pediatric anesthesia care, children with X-linked adrenoleukodystrophy can undergo procedures under anesthesia in sedation units and regular operating rooms with low overall anesthesia risk.

Method of detection of thyroid nodules: correlation with frequency of fine-needle aspiration and malignancy rate.

BACKGROUND: Thyroid nodules are commonly found by screening, and the clinical implications are unclear. METHODS: We retrospectively studied 460 patients who were evaluated for thyroid nodules. Medical records were queried to determine how the nodules were detected. We compared the rates of fine needle aspiration (FNA) and malignancy between nodules detected clinically, incidentally on imaging, or by screening. RESULTS: Nodules were detected clinically in 184 patients (40%), incidentally in 121 patients (26%), and by screening in 155 patients (34%). The rates of FNA and malignancy were lower for patients with nodules detected by screening (28% and 1%, respectively), compared to patients with clinically apparent nodules (75% and 15%) and patients with incidental nodules (69% and 8% [P < .001]). CONCLUSION: Thyroid nodules detected via screening has a lower rate of FNA and is less likely to be diagnosed as a malignancy compared to nodules detected clinically or incidentally on imaging. Thyroid ultrasound examinations should be reserved for nodules that are clinically apparent or to evaluate nodules found incidentally on imaging.

A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes. METHODS: We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn. RESULTS: We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut. CONCLUSIONS: This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD.

Patterns of care for clinically distinct segments of high cost Medicare beneficiaries.

BACKGROUND: Efforts to improve the efficiency of care for the Medicare population commonly target high cost beneficiaries. We describe and evaluate a novel management approach, population segmentation, for identifying and managing high cost beneficiaries. METHODS: A retrospective cross-sectional analysis of 6,919,439 Medicare fee-for-service beneficiaries in 2012. We defined and characterized eight distinct clinical population segments, and assessed heterogeneity in managing practitioners. RESULTS: The eight segments comprised 9.8% of the population and 47.6% of annual Medicare payments. The eight segments included 61% and 69% of the population in the top decile and top 5% of annual Medicare payments. The positive-predictive values within each segment for meeting thresholds of Medicare payments ranged from 72% to 100%, 30% to 83%, and 14% to 56% for the upper quartile, upper decile, and upper 5% of Medicare payments respectively. Sensitivity and positive-predictive values were substantially improved over predictive algorithms based on historical utilization patterns and comorbidities. The mean [95% confidence interval] number of unique practitioners and practices delivering E&M services ranged from 1.82 [1.79-1.84] to 6.94 [6.91-6.98] and 1.48 [1.46-1.50] to 4.98 [4.95-5.00] respectively. The percentage of cognitive services delivered by primary care practitioners ranged from 23.8% to 67.9% across segments, with significant variability among specialty types. CONCLUSIONS: Most high cost Medicare beneficiaries can be identified based on a single clinical reason and are managed by different practitioners. IMPLICATIONS: Population segmentation holds potential to improve efficiency in the Medicare population by identifying opportunities to improve care for specific populations and managing clinicians, and forecasting and evaluating the impact of specific interventions.

Utilizing quantitative measures of visceral adiposity in evaluating trauma patient outcomes.

INTRODUCTION: Body mass index (BMI) has commonly been used as a parameter to assess obesity in trauma patients. However, the variability of height and weight data in trauma patients limits the use of BMI as an accurate assessment tool in the trauma population. Quantitative radiologic measurements of visceral adiposity is an accurate method for assessing obesity in patients but requires further analysis before it can be accepted as a measurement tool for trauma patients. METHODS: A retrospective review of trauma cases with pre-operative CT scan from 2008 to 2015 produced 57 patients for evaluation. Preoperative BMI was calculated using measured height (m2) and weight (kg). Radiologic measurements of adiposity were obtained from preoperative CT scans using OsiriX DICOM viewer software. Visceral fat areas (VFA) and subcutaneous fat areas (SFA) were measured from a single axial slice at the level of L4-L5 intervertebral space. RESULTS: No statistically significant results were found relating visceral fat:subcutaneous fat ratios to length of stay or post-operative complications. Initial clinical observations noting an increased incidence of complications among patients with a V/S ≥ 0.4 demonstrates a possible link between obesity and poor outcomes in trauma patients. A statistically significant correlation was noted between length of stay, peri-nephric fat and injury severity score. DISCUSSION AND CONCLUSION: Our pilot study should be viewed as the foundation for a larger prospective study, utilizing quantitative measurements of visceral adiposity to assess outcomes in trauma patients.

High C-Reactive Protein Is Associated with Poor Sleep Quality Independent of Nocturnal Symptoms in Patients with Inflammatory Bowel Disease.

BACKGROUND: Sleep disruption is common in inflammatory bowel diseases (IBD). However, studies demonstrating a similar prevalence in irritable bowel syndrome suggest that nighttime disruption due to diarrhea and abdominal pain may be key drivers of poor sleep quality. Whether inflammation is associated with poor sleep independently has not been examined previously. METHODS: This single-center study included subjects with IBD recruited to an ongoing prospective registry who completed a questionnaire assessing sleep quality and mood. Inflammatory marker levels [C-reactive protein (CRP), erythrocyte sedimentation rate] and clinical disease activity including nighttime disruption on the day of enrollment were obtained from the medical record. Logistic regression models were used to identify predictors of sleep quality. RESULTS: The study included 131 subjects (72 women) with a median age of IBD diagnosis of 25 years. Twenty-three subjects (19 %) had a high C-reactive protein level (≥8 mg/dL). Poor sleep was more common in those with high CRP levels than with normal values (70 vs. 39 %, p = 0.009). This association remained significant on multivariate analysis [Odds ratio (OR) 4.12, 95 % confidence interval (CI) 1.38-12.29]. Adjusting for the presence of nighttime disruption did not significant alter this association (OR 3.16, 95 % CI 1.01-9.90). High CRP correlated with poor sleep even in patients not experiencing nocturnal symptoms (n = 101, OR 4.89, 95 % CI 1.24-19.36). CONCLUSION: High CRP is associated with poor sleep quality in IBD independent of the presence of nighttime disruptions, suggesting that a relationship exists between circulating inflammatory markers and sleep.

Early life environment and natural history of inflammatory bowel diseases.

BACKGROUND: Early life exposures may modify risk of inflammatory bowel diseases (IBD; Crohn's disease (CD), ulcerative colitis (UC)). However, the relationship between early life exposures and natural history of IBD has not been previously examined. METHODS: This single center study included patients with CD or UC recruited in a prospective IBD registry. Enrolled patients completed a detailed environmental questionnaire that assessed various early life environmental exposures. Our primary outcome was requirement for disease-related surgery in CD and UC. Logistic regression models defined independent effect of early life exposures, adjusting for potential confounders. RESULTS: Our study included 333 CD and 270 UC patients. Just over half were female with a median age at diagnosis of 25 years. One-third of the cohort had history of bowel surgery (31%) and nearly half had used at least one biologic agent (47%). Among those with CD, being breastfed was associated with reduced risk of CD-related surgery (34% vs. 55%), while childhood cigarette smoke exposure was associated with increased risk. On multivariate analysis, history of being breastfed (odds ratio (OR) 0.21, 95% confidence interval [CI] 0.09-0.46) and cigarette smoke exposure as a child (OR 2.17, 95% CI 1.10-4.29) remained independently associated with surgery. None of the early life variables influenced disease phenotype or outcome in UC. CONCLUSION: A history of being breastfed was associated with a decreased risk while childhood cigarette smoke exposure was associated with an increased risk of surgery in patients with CD. Further investigation to examine biological mechanisms is warranted.

Male chronic pelvic pain syndrome and the role of interdisciplinary pain management.

INTRODUCTION: This paper is a team collaboration which aims to describe the multidisciplinary chronic pelvic pain (CPP) service for men in a major London teaching hospital. METHOD: Evidence from the European Association for Urology Guidelines and the small pool of relevant psychological literature is reviewed as well as results from our pelvic pain programme (LINK) in association with a description of the programme. RESULTS: Treatment targets for men with CPP are outlined. The roles of the consultant in pain management, clinical nurse specialist, clinical psychologist and specialist physiotherapist in delivering treatment are described. This includes the journey from initial consultation through treatment options. Finally, we describe our pelvic pain programme (LINK) which aims to deliver an effective multidisciplinary intervention via single sex groups. CONCLUSION: This programme links all significant treatment dimensions as well as connecting groups of patients to reduce their sense of isolation. Evidence is presented from the formal evaluation of the programme.

Molecularly mediated thin film assembly of nanoparticles on flexible devices: electrical conductivity versus device strains in different gas/vapor environment.

The ability to precisely control nanoparticle-enabled electrical devices for applications involving conformal wrapping/bending adaptability in various complex sensing environments requires an understanding of the electrical correlation with the device strain and exposure to the molecular environment. This report describes novel findings of an investigation of molecularly mediated thin film assembly of gold nanoparticles on flexible chemiresistor devices under different device strains and exposure molecules. Both theoretical and experimental data have revealed that the electrical conductivity of the nanoparticle assembly depends on a combination of the device strain and the exposure molecules. Under no device strain, the electrical conductivity is sensitive to the molecular nature in the exposure environment, revealing a clear increase in electrical conductivity with the dielectric constant of vapor molecules. Under small device strains, the electrical conductivity is shown to respond sensitively to the strain directions (tensile vs compressive strain) and also to the dielectric constant of the vapor molecules in a way resembling the characteristic under no device strain. Under large device strains, the electrical conductivity is shown to respond to the difference in dielectric constant of the vapor molecules but, more significantly, to the device tensile and compressive strains than those under small device strains. This combination of device strain and dielectric characteristic is also dependent on the orientation of the microelectrode patterns with respect to the device strain direction, a finding that has important implications to the design of flexible arrays for a complex sensing environment.

Health risk behaviors in parentally bereaved youth.

OBJECTIVE: To investigate whether parentally bereaved offspring are more likely to engage in health risk behaviors than nonbereaved control offspring. DESIGN: Controlled population-based study. SETTING: Bereaved families were recruited from coroner records and by advertisement. Control families were recruited using random-digit dialing and by advertisement. PARTICIPANTS: At 9.0 months after the death, 186 offspring aged 7 to 25 years of parents who died of suicide, accident, or sudden natural death were compared with 167 nonbereaved control offspring. MAIN OUTCOME MEASURES: The association of bereavement with health risk behaviors was examined. The prevalences of health risk behaviors on the Youth Risk Behavior Questionnaire were compared between bereaved and nonbereaved offspring. Risk behaviors surveyed were related to unintentional injury, violence, sexual behavior, cigarette smoking, and alcohol or other drug use. RESULTS: No statistically significant difference was noted in the examined health risk behaviors between bereaved and nonbereaved offspring. CONCLUSIONS: Bereaved offspring did not engage in more health risk behaviors compared with nonbereaved offspring. Primary care physicians counseling youth should inquire about health risk behaviors in general.

Graft weight/recipient weight ratio: how well does it predict outcome after partial liver transplants?

Partial graft liver recipients with graft weight/recipient weight (GW/RW) ratios < 0.8% are thought to have a higher incidence of postoperative complications, including small-for-size syndrome (SFSS). We analyzed a cohort of such recipients and compared those with GW/RW < 0.8% to those with GW/RW >or= 0.8%. Between 1999 and 2008, 107 adult patients underwent partial graft liver transplants: 76 from live donors [living donor liver transplantation (LDLT)] and 31 from deceased donors [split liver transplantation (SLT)]. Of these, 22 had GW/RW < 0.8% (12 with LDLT and 10 with SLT), and 85 had GW/RW >or= 0.8% (64 with LDLT and 21 with SLT). The baseline demographics and median length of follow-up were similar. SFSS developed in 3 recipients with GW/RW < 0.8% (13.6%) and in 8 recipients with GW/RW >or= 0.8% (9.4%; P = not significant). Other early complications were similar between the 2 groups. Inflow modification with splenic artery occlusion was performed in 13 recipients: 7 with GW/RW < 0.8% and 6 with GW/RW >or= 0.8%. Graft survival at 1 year post-transplant did not differ (91% versus 92%; P = not significant). In conclusion, GW/RW did not appear to be the only determinant of outcome after partial liver transplantation. Using techniques such as inflow modification may help to prevent some of the problems seen with smaller grafts.

Delayed splenic artery occlusion for treatment of established small-for-size syndrome after partial liver transplantation.

We looked at the impact of delayed splenic artery occlusion (SAO) on recipients with established small-for-size syndrome (SFSS) after partial graft liver transplantation [either from a living donor (LD) or split from a deceased donor (DD)]. Between 1999 and 2007 we performed a total of 100 partial liver transplantations in adult recipients: 66 LD transplantations and 34 DD split transplantations. Of these, 7 (7%) developed SFSS, diagnosed by the clinical features of cholestasis, coagulopathy, and ascites. Mean graft weight/recipient weight (GW/RW) ratio in these 7 recipients was 0.94%. Five of these 7 recipients underwent relaparotomy at a mean of 10 days post-transplantation to rule out a technical complication, and then intraoperative splenic artery ligation was performed. The other 2 recipients were treated radiologically by splenic artery coiling-at 9 and 13 days post-transplantation. Median serum bilirubin at the time of the splenic artery procedure was 20 mg/dL; by 3 weeks postprocedure this had decreased to 2.5 mg/dL. Of the 7 recipients with SFSS, 6 improved and eventually obtained normal graft function; 1 recipient did not improve and ultimately underwent retransplantation because of persistent cholestasis and failure to thrive. Delayed SAO represents a potential option for the treatment of recipients with established SFSS after partial liver transplantation.

Lower levels of whole blood LPS-stimulated cytokine release are associated with poorer clinical outcomes in surgical ICU patients.

BACKGROUND: In vitro pretreatment of human monocytes with lipopolysaccharide (LPS) induces "endotoxin tolerance" with blunted TNF and IL-6 release to rechallenge with LPS. The pro-inflammatory cytokines TNF and IL-6 are important mediators in sepsis. A high IL-6 concentration has been used as a marker of infection severity, but IL-6 may also have beneficial effects as an acute-phase protein. We sought to address two questions: (a) What is the relationship between TNF and IL-6 release? (b) Is the clinical outcome different for intensive care unit (ICU) patients with ex vivo characteristics of endotoxin tolerance (low levels of ex vivo LPS-stimulated cytokine release)? MATERIALS AND METHODS: Heparinized whole blood was obtained from 62 surgical ICU patients and 15 control subjects and incubated for 3 h at 37 degrees C in the presence or absence of 10 ng/mL LPS. Concentrations of TNF and IL-6 were measured in plasma samples using an enzyme-linked immunosorbent assay (pg/mL). Clinical data on ICU length of stay (LOS), ventilator days, white blood cell count (WBC), and documented clinical infection were obtained by chart review. Outcome parameters for patients with low ex vivo LPS-stimulated cytokine release (low = IL-6 < 3000 pg/mL and TNF <2100 pg/mL) were compared to patients with Normal/High concentrations of cytokines. RESULTS: Cytokines were essentially undetectable in ICU patients or controls without LPS stimulation, however a range of values was measured for LPS-stimulated release in both ICU patients (IL-6, 7847 +/- 857 pg/mL; TNF, 4390 +/- 457 pg/mL) and controls (IL-6, 7704 +/- 793 pg/mL; TNF, 6706 +/- 715 pg/mL). There were no differences in age between High/Normal concentrations of cytokines compared to the Low cytokine group, however there were significant differences in WBC, cytokine concentrations, ICU LOS, incidence of clinical infection, and mortality. The Low group also required an average of 6.9 more days of mechanical ventilation (p < 0.05). LPS-stimulated TNF release seemed to correlate better with the observed mortality than did IL-6 release. CONCLUSION: The data suggest that ICU patients with characteristics of endotoxin tolerance (low LPS-stimulated cytokine release capacity) have significantly poorer clinical outcomes. Ex vivo LPS-stimulated whole blood cytokine production may be useful to identify ICU patients with severe sepsis.

Is laparoscopic umbilical hernia repair with mesh a reasonable alternative to conventional repair?

BACKGROUND: Laparoscopic mesh repair has been advocated as treatment of choice for ventral hernias. The term "ventral hernia" refers to a variety of abdominal wall defects and laparoscopic papers have not reported defect specific analysis. The purpose of this study was to determine any advantages to laparoscopic mesh repair of umbilical hernias. METHODS: A retrospective review (January 1998 to April 2001) was made of patients undergoing umbilical hernia repair. Patients were categorized into three groups: laparoscopic repair with mesh, open repair with mesh, and open repair without mesh. Comparative analysis was performed. RESULTS: One-hundred and sixteen umbilical hernia repairs were performed in 112 patients: 30 laparoscopic mesh repairs, 20 open mesh repairs, and 66 open nonmesh repairs. The laparoscopic technique was used for larger defects and took more time with a trend toward fewer postoperative complications and recurrences. CONCLUSIONS: Laparoscopic umbilical hernia repair with mesh presents a reasonable alternative to conventional methods of repair.