Geffen Kleinstern

Hypoglycemia During Oral Glucose Tolerance Test Among Post-Bariatric Surgery Pregnant Patients: Incidence and Perinatal Significance

BACKGROUND While hypoglycemia during an oral glucose tolerance test (OGTT) has been shown to occur in a considerable portion of nonpregnant post-bariatric surgery (BS) patients, its incidence among pregnant post-BS patients evaluated for gestational diabetes has only been sparsely studied. OBJECTIVES We investigated OGTT results and pregnancy outcomes in pregnant women who underwent 3 types of bariatric procedures before pregnancy. SETTING A university hospital. METHODS From medical records, data were collected on glucose measurements during a 100-g, 3-hour OGTT, as well as maternal and fetal outcomes. RESULTS Of 119 post-BS pregnant patients included in the study, 55 underwent laparoscopic sleeve gastrectomy, 34 laparoscopic adjustable gastric banding, and 30 laparoscopic Roux-en-Y gastric bypass surgery. Hypoglycemia (<55 mg/dL) was encountered in 59 (49.6%) patients during the OGTT. Among them, the nadir plasma glucose levels occurred 2 hours after glucose ingestion in 25 (42.4%) and after 3 hours in 34 (57.6%), with a median value of 47 (44-52) mg/dL. The risk of hypoglycemia was higher among women with prior laparoscopic Roux-en-Y gastric bypass surgery (83.3%) than among those with prior laparoscopic sleeve gastrectomy (54.5%; P = .009) or laparoscopic adjustable gastric banding (11.8%; P<.0001). Time from surgery to conception was significantly shorter among women with evidence of hypoglycemia during OGTT (median 711 versus 1246 days, P = .002). Compared with patients without evidence of hypoglycemia, patients who experienced hypoglycemia had lower rates of gestational diabetes (P = .03) but higher proportions of low birth weight (P = .01) and small for gestational age infants (P = .03). CONCLUSIONS Because hypoglycemia is common during OGTT among post-BS parturients, other diagnostic methods should be considered in this setting. The association found between hypoglycemia and poor fetal growth warrants investigation as to whether interventions to prevent hypoglycemia will improve fetal outcome.

Factors related to the development of acquired von Willebrand syndrome in patients with essential thrombocythemia and polycythemia vera

OBJECTIVE We characterized acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) and polycythemia vera (PV) patients. METHODS A review of patients with ET or PV evaluated for AVWS. RESULTS Of 116 patients with ET, 64 (55%) developed AVWS; of 57 with PV, 28 (49%) developed AVWS. Median platelet counts of ET and PV patients who developed AVWS were 920×109/L and 679×109/L, respectively (P=0.01). Of patients who developed AVWS, 69.5% had platelet counts below 1000×109/L. Bleeding was more common in patients with AVWS, among both ET and PV patients (P<0.001). VWF:RCo levels and VWF:RCo/VWF:Ag ratio were lower among JAK2 V617F positive- vs. JAK2 V617F negative- ET patients (P=0.02 and P=0.002, respectively); whereas VWF:Ag levels were comparable (P=0.96). ET patients harboring the JAK2 V617F mutation were more likely to develop AVWS than were calreticulin-positive patients (70.3% vs. 45.7%, P=0.02), despite lower platelet counts (median 773 vs. 920×109/L, P=0.05). In multivariable analysis, younger age (P=0.002), platelet count (P<0.001), hemoglobin level (P=0.01) and JAK2 V617F mutation (P=0.01) independently predicted the development of AVWS among ET patients; whereas only platelet count predicted its development among PV patients (P<0.001). CONCLUSION Among ET and PV patients, AVWS was common and associated with higher bleeding rates and higher platelet count; nonetheless, most AVWS patients had platelet counts under 1000×109/L. Thus, AVWS screening should be included in routine assessment of ET and PV patients. Among ET patients, JAK2 V617F was a main driver for the development of AVWS.

Ethnic variation in medical and lifestyle risk factors for B cell non-Hodgkin lymphoma: A case-control study among Israelis and Palestinians

Background Risk factors for B-cell non-Hodgkin lymphoma (B-NHL) have not been assessed among Palestinian Arabs (PA) and Israeli Jews (IJ). Methods In a case-control study we investigated self-reported medical and lifestyle exposures, reporting odds ratios (ORs) and 95% confidence intervals [CIs], by ethnicity, for overall B-NHL and subtypes. Results We recruited 823 cases and 808 healthy controls. Among 307 PA/516 IJ B-NHL cases (mean age at diagnosis = 51 [±17] versus 60 [±15] years, respectively) subtype distributions differed, with diffuse large B-cell lymphoma (DLBCL) being prominent among PA (71%) compared to IJ (41%); follicular lymphoma (FL), was observed in 14% versus 28%, and marginal zone lymphoma, in 2% versus 14%, respectively. Overall B-NHL in both populations was associated with recreational sun exposure OR = 1.43 [CI:1.07–1.91], black hair-dye use OR = 1.70 [CI:1.00–2.87], hospitalization for infection OR = 1.68 [CI:1.34–2.11], and first-degree relative with hematopoietic cancer, OR = 1.69 [CI:1.16–2.48]. An inverse association was noted with alcohol use, OR = 0.46 [CI:0.34–0.62]. Subtype-specific exposures included smoking (FL, OR = 1.46 [CI:1.01–2.11]) and >monthly indoor pesticide use (DLBCL, OR = 2.01 [CI:1.35–3.00]). Associations observed for overall B-NHL in PA only included: gardening OR = 1.93 [CI:1.39–2.70]; history of herpes, mononucleosis, rubella, blood transfusion (OR>2.5, P<0.01 for all); while for IJ risk factors included growing fruits and vegetables, OR = 1.87 [CI:1.11–3.15]; and self-reported autoimmune diseases, OR = 1.99 [CI:1.34–2.95]. Conclusions In these geographically proximate populations we found some unique risk factors for B-NHL. Heterogeneity in the observed associations by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by histology infer specific etiologic factors for lymphoma subtypes.

Assessment of procoagulant potential in patients with reactive thrombocytosis and its association with platelet count

We aimed to determine hemostatic changes and characterize the procoagulant potential among patients with reactive thrombocytosis (RT).

Assessment of the procoagulant potential after laparoscopic sleeve gastrectomy: a potential role for extended thromboprophylaxis

BACKGROUND Bariatric surgery is associated with increased thromboembolic risk, which may extend well beyond hospital stay. The hemostatic mechanisms implicated in this risk are not well established. OBJECTIVES We aimed to determine the dynamics of hemostatic changes and procoagulant potential among patients undergoing laparoscopic sleeve gastrectomy, during both the early and late postoperative periods. SETTING A university hospital. METHODS Patients who underwent laparoscopic sleeve gastrectomy were recruited consecutively to this study. Blood samples were taken preoperatively, before discharge (postoperative day [POD] 3), and at the first follow-up visit (POD10). All samples were tested for complete blood count, C-reactive protein, von Willebrand factor, factor VIII, fibrinogen, and thrombin generation. RESULTS The median preoperative body mass index of the 26 participants was 41.3 (38.7-43.3) kg/m2. Compared with preoperative evaluation, fibrinogen, von Willebrand factor antigen and activity, and factor VIII levels were significantly higher at POD3 and POD10 (P<.0001 for all comparisons). Peak thrombin levels and endogenous thrombin potential (ETP) were higher at POD3 (P = .005 for both comparisons) and POD10 (P = .0009 and<.0001) compared with baseline. ETP and peak thrombin, as well as fibrinogen, von Willebrand factor, and factor VIII levels, were comparable between POD3 and POD10. Multivariate analysis showed that the only predictor of postoperative ETP was the preoperative ETP level (β = .55, P = .007). CONCLUSIONS As determined by thrombin generation, laparoscopic sleeve gastrectomy was associated with hypercoagulability, which persisted during POD10. This finding suggests a possible benefit of extended thromboprophylaxis. Nevertheless, our results should be interpreted with caution due to the lack of a control group.

Presence of autoimmune disease affects not only risk but also survival in patients with B-cell non-Hodgkin lymphoma

Although autoimmune diseases (AIDs) are known to predispose to non‐Hodgkin lymphoma (NHL), their association with NHL prognosis has rarely been investigated. We examined associations between autoimmunity and B‐cell NHL onset by comparing AID history (determined by self‐report and medication review and supplemented by chart review where possible) among 435 adult B‐NHL patients in Hadassah‐Hebrew University Medical Center, diagnosed 2009‐2014, and 414 age‐and‐sex frequency‐matched controls. We examined AIDs as a whole, B‐ and T‐cell–mediated AIDs, and autoimmune thyroid diseases. Among cases, we used Kaplan‐Meier and Cox regression models to assess the association of AID with overall survival and relapse‐free survival, adjusting for prognostically important patient and disease characteristics such as Ki67% staining, International Prognostic Index, rituximab treatment, and histological subgroup.

Factors associated with thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

We investigated the risk factors, incidence, and role of thromboprophylaxis in the development of thrombosis following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

The effect on thrombin generation and anti-Xa levels of thromboprophylaxis dose adjustment in post-cesarean obese patients - A prospective cohort study

OBJECTIVE To examine the laboratory anticoagulant effect of two thromboprophylactic low-molecular weight heparin (LMWH) regimens in post-cesarean obese patients. METHODS A prospective cohort study, performed during 2017-2018 at a university hospital, of post-cesarean obese (>90 kg) patients receiving 40 mg/day (n = 30) or 60 mg/day (n = 30) enoxaparin, and a control group of non-obese (n = 30) post-cesarean patients receiving 40 mg/day enoxaparin. Thrombin generation and anti-Xa were measured twice on the third postoperative day: prior to and 3.5-4 h following the third LMWH dose. RESULTS Age, parity, weight and body mass index were comparable between the obese study groups. Compared to the control non-obese group, the 40 mg obese and 60 mg obese groups showed increased baseline thrombin generation: medians 491, 581, 571 nM, respectively (P = 0.001 and P = 0.04, respectively). At peak LMWH activity, thrombin generation was higher in the 40 mg than in the 60 mg obese and control groups: medians 2599, 2391, 2229 nM, respectively (P = 0.01 and P < 0.0001, respectively); and thrombin generation was comparable between the 60 mg obese and the control groups (P = 0.58). Similarly, a significantly lower proportion of patients in the 40 mg obese group (10%) had anti-Xa levels within the recommended prophylactic range (0.2-0.5 IU/mL) than in the other groups (P < 0.0001 for both comparisons). CONCLUSION As determined by thrombin generation and anti-Xa testing, post-cesarean obese patients have an increased procoagulant potential, which was diminished only in those receiving higher dosages of LMWH. These findings support the need for clinical evaluation of LMWH dose adjustment in this setting.

The effect of surgery-to-conception interval on pregnancy outcomes after sleeve gastrectomy

BACKGROUND The optimal timing of pregnancy after bariatric surgery has not been established, with data limited regarding laparoscopic sleeve gastrectomy (LSG), currently the most common bariatric operation performed. OBJECTIVES We explored associations of the surgery-to-conception interval with pregnancy outcomes after LSG. SETTING A university hospital. METHODS We assessed pregnancy outcomes in relation to the surgery-to-conception interval for all women who underwent LSG and delivered during 2006 to 2018. RESULTS Of 154 patients, 67 (43.5%) conceived within the first 18 months postoperatively (early-pregnancy group), whereas 87 (56.5%) conceived later (late-pregnancy group). The median surgery-to-conception interval was 390 (interquartile range 247-459) days in the early-pregnancy group and 1104 (8527-1548) days in the late-pregnancy group. Compared with the early-pregnancy group, the late-pregnancy group had higher gestational weight gain (median 11 versus 8 kg, P < .001) and lower hemoglobin levels in early pregnancy (12.3 versus 12.6 g/dL, P = .03) and after delivery (10.0 versus 10.4 g/dL, P = .02). Other maternal and perinatal outcomes were similar between the groups, including the proportion of small-for-gestational-age infants (11.9% versus 14.9%, P = .64) for those who conceived within or later than 18 months after surgery. Similar rates of small-for-gestational-age infants were found between those who conceived within or ≥12 months after surgery (P = 1.0). CONCLUSIONS Timing of pregnancy after LSG was found not to be associated with pregnancy outcomes. Together with documentations of a similar safety profile of pregnancy occurring earlier or later in the postoperative course, these data should reassure women who do not wish to delay conception after surgery.

The long-term effect of pregnancy on weight loss after sleeve gastrectomy

BACKGROUND Pregnancy outcomes after bariatric surgery have been addressed extensively; however, the impact of pregnancy on long-term outcomes after bariatric surgery has only been sparsely studied. OBJECTIVES We explored the effects of pregnancy on weight loss outcomes after laparoscopic sleeve gastrectomy (LSG). SETTING University hospital. METHODS A cross-sectional case-control study. Eighty women who became pregnant after LSG were matched by preoperative body mass index, age, and follow-up duration to 80 post-LSG patients who did not conceive after surgery (control group). RESULTS The median follow-up duration was 5.2 years for the study group and 5.3 years for the control group (P = .73). For the study group, the median time from surgery to conception was 508 (interquartile range 372-954) days and the median gestational weight gain was 9 (6-12) kg. Comparing the study with the control group, median percentage total weight loss was similar, 31% versus 30% (P = .77); as was percentage excess weight loss (EWL%) 72% versus 71% (P = .77). For the study group, a multivariable analysis showed EWL% at the end of follow-up to be directly correlated with the lowest EWL% achieved before pregnancy (β = .78, P < .0001), and inversely correlated with time lapsed from surgery (β = -.26, P < .0001); yet EWL% was not found to be associated with surgery-to-conception time interval, gestational weight gain, breastfeeding, co-morbidities, smoking, occupational status, physical activity, and dietary habits. CONCLUSIONS Pregnancy after LSG does not affect long-term weight results. Coupled with the positive reports of improved pregnancy outcomes after bariatric surgery, these data should reassure women who wish to conceive after surgery.