A risk-adjusted analysis of drain use in pancreaticoduodenectomy: Some is good, but more may not be better.

BACKGROUND: Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF. METHODS: The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach. RESULTS: A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P < .001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone. CONCLUSION: In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

Cerebral hemorrhage in the LVAD patient: A case series and literature review.

INTRODUCTION: A left ventricular assist device (LVAD) is used in certain heart failure cases, but LVADs can have significant neurological complications including intracranial hemorrhages (ICH). Prediction and management of ICHs is challenging due to medical comorbidities and blood thinners. METHODS: A retrospective review of LVAD patients with ICHs from 2015 to 2019 was performed. The data included demographics, premorbid conditions, hemorrhage type, treatments, and outcomes. RESULTS: Twenty-two patients were included with a median age of 53 and a median time of 16 months from LVAD insertion to ICH. All patients were on blood thinners prior to ICH. The hemorrhage type included subarachnoid hemorrhage (41 %), intracerebral hemorrhage (32 %), and subdural hematomas (23 %). The blood-thinning agent was reversed in 64 % of patients with a median of 3.5 days prior to resumption of these medications. Ten re-hemorrhages occurred with 4 of these hemorrhages within two weeks of anticoagulation resumption. Open cranial surgery was performed in 32 % of all patients, and the mortality was 41 %. CONCLUSIONS: Management of these patients is challenging with a relatively high rate of re-hemorrhage and need for surgical intervention. Despite maximal management, the mortality remains high.

Associations of the melanocortin 3 receptor C17A + G241A haplotype with body composition and inflammation in African-American adults.

BACKGROUND: The MC3R haplotype C17A + G241A, which encodes a partially inactivated receptor, has high prevalence in individuals of predominately African ancestry. In pediatric cohorts, homozygosity for this common variant has been associated with obesity, reduced lean mass, and greater fasting insulin. However, metabolic and body composition measures have not been well studied in adults with this haplotype. METHODS: A convenience sample of 237 healthy African-American adult volunteers was studied. TaqMan assays were used to genotype MC3R variants. Labs were drawn in the morning in the fasted state. Body composition data was obtained via dual-energy X-ray absorptiometry. An analysis of covariance was used to examine the associations of genotype with metabolic and body composition measures controlling for age and sex. RESULTS: Individuals homozygous for the MC3R C17A + G241A haplotype had significantly greater body mass index, fat mass, fat mass percentage, and C-reactive protein, with reduced lean mass percentage as compared to heterozygous and wild-type participants (all ps < 0.05); fasting insulin was marginally nonsignificant between groups (p = 0.053). After adjusting for fat mass, laboratory differences no longer remained significant. CONCLUSIONS: Homozygosity for MC3R C17A + G241A is associated with increased adiposity in African-American adults. Further studies are needed to elucidate the mechanisms behind these associations.

Subcutaneous adipose tissue imaging of human obesity reveals two types of adipocyte membranes: Insulin-responsive and -nonresponsive.

In adipose tissue, resistance to insulin's ability to increase glucose uptake can be induced by multiple factors, including obesity. Impaired insulin action may take place at different spatial loci at the cellular or subcellular level. To begin to understand the spatial response to insulin in human subcutaneous adipose tissue (hSAT), we developed a quantitative imaging method for activation of a major signaling node in the glucoregulatory insulin signaling pathway. After treatment with insulin or control media, biopsied tissues were immunostained for Akt phosphorylation at Thr-308/9 (pAkt) and then imaged by confocal fluorescence microscopy automated to collect a large grid of high resolution fields. In hSAT from 40 men and women with obesity, substantial heterogeneity of pAkt densities in adipocyte membranes were quantified in each image mosaic using a spatial unit of at least twice the size of the point spread function. Statistical analysis of the distribution of pAkt spatial units was best fit as the weighted sum of two separate distributions, corresponding to either a low or high pAkt density. A "high pAkt fraction" metric was calculated from the fraction of high pAkt distributed units over the total units. Importantly, upon insulin stimulation, tissues from the same biopsy showed either a minimal or a substantial change in the high pAkt fraction. Further supporting a two-state response to insulin stimulation, subjects with similar insulin sensitivity indices are also segregated into either of two clusters identified by the amount of membrane-localized pAkt.

Circulating early- and mid-pregnancy microRNAs and risk of gestational diabetes.

AIMS: Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex. METHODS: In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen for potential roles in pregnancy course and complications (miR-126-3p, -155-5p, -21-3p, -146b-5p, -210-3p, -222-3p, -223-3p, -517-5p, -518a-3p, and 29a-3p) using qRT-PCR. Logistic regression models adjusted for gestational age at blood draw (GA) were fit to compare circulating miRNAs between cases and controls. We repeated analyses among overweight/obese (ppBMI≥25kg/m2) or lean (ppBMI<25kg/m2) women, and women with male or female offspring separately. RESULTS: Mean age was 34.3years (cases) and 32.9years (controls). GA-adjusted miR-155-5p (ß=0.260/p=0.028) and -21-3p (ß=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p (ß=0.266/p=0.068) and miR-517-5p (ß=0.196/p=0.074) were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs (miR-155-5p, -21-3p, -146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses (all p<0.05). CONCLUSIONS: Circulating early-mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring. This area has potential to clarify mechanisms underlying GDM pathogenesis and identify at-risk mothers earlier in pregnancy.

Instability of the first metatarsal-cuneiform joint: diagnosis and discussion of an independent pain generator in the foot.

BACKGROUND: First metatarsocuneiform (MC) instability is recognized as a pathologic contributor to hallux valgus. There are no studies identifying the first MC joint as an independent pain generator in the foot that may require surgical arthrodesis for its management. MATERIALS AND METHODS: The authors reviewed the records of all patients with this newly described pathology in the first MC joint. There were 61 patients with 85 feet who underwent a fluoroscopically guided local anesthetic injection into the first metatarsocuneiform joint to assess pain relief. Patient's complaints, physical exam findings, treatment decisions, patient characteristics, and radiographic findings were evaluated. RESULTS: Seventy-nine percent of patients (67/85) injected had relief of their symptoms. Eight or these 67 patients were eventually treated with first MC arthrodesis with complete relief of symptoms. The average time from onset of symptoms to presentation was 21 (range, 1 to 72) months. Eighty-five percent of feet (72/85) had multiple previous diagnoses. Radiographic plantar widening of the first M-C joint on weightbearing views was inconsistent with pathology. CONCLUSION: The first MC joint is an independent pain generator in the foot that can have variable presentations. Radiographic data can often be helpful, but clinical exam findings are paramount in the diagnosis. Fluoroscopically-guided long acting local anesthetic injections of this joint are helpful in the diagnosis, especially in the patient with multiple possible pain generators in the foot and ankle. Failure to recognize the first MC joint as a source of pain may lead to delay in treatment, misdiagnosis, and mistreatment of foot pathology.