Familial hypocalciuric hypercalcemia as a differential diagnosis of primary hyperparathyroidism with negative images

Introduction. Familial hypocalciuric hypercalcemia is a rare inherited calcium metabolism disorder in which an alteration of the parathyroid hormone secretion set-point causes hypercalcemia with relative hypocalciuria. Some data suggest that its prevalence is around 74.1 per 100,000 inhabitants. Often, patients are asymptomatic. However, they can develop mild symptoms and an overactive parathyroid adenoma, its main differential diagnosis. The objective was to describe a patient’s case and highlight the importance of clinical suspicion and diagnosis to avoid unnecessary surgical neck explorations for parathyroid adenomas. Case report. This is the case of a 40-year-old man with a biochemical profile compatible with primary hyperparathyroidism with anatomical and functional images negative for adenoma and a calcium/creatinine clearance ratio below 0.001, considering familial hypocalciuric hypercalcemia. Genetic studies evidence a mutation in the calcium sensor receptor gene and confirm the diagnosis. Discussion. Familial hypocalciuric hypercalcemia’s main differential diagnosis is an overactive parathyroid adenoma. For both, mild or no symptoms may be present; serum calcium exceeds the upper limit, and parathormone is more than 25pg/ml. The calcium/creatinine clearance ratio should be used to differentiate one from the other and avoid unnecessary surgical neck explorations. Besides the lack of information on this topic, evidence supports the use of calcimimetics to treat symptomatic hypercalcemia. Conclusions. Patients with mild hypercalcemia with parathyroid hormone readings above 25pg/ml and a calcium/creatinine clearance ratio below 0.001, or patients with primary hyperparathyroidism with negative imaging, should not undergo surgical neck explorations. In these cases, familial hypocalciuric hypercalcemia is a reliable diagnosis; Cinacalcet may be administered in cases of symptomatic hypercalcemia.

374 Volume of contrast to creatinine clearance ratio predicts early mortality and AKI after TAVI

Aims The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. Methods and results A large retrospective multicentre cohort of 1381 patients treated with TAVI was analysed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and one year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (HR: 1.16, 95% CI: 1.09–1.22, P < 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (OR: 1.18, 95% CI: 1.08–1.28, P < 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01–3.60, P = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21–3.11, P = 0.006) but not CV/CrCl was associated with the risk of 1-year mortality after TAVI. Conclusions CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.

Predictive role of lymphoscintigraphy undergoing lymphovenous anastomosis in patients with lower extremity lymphedema: a preliminary study

Background We investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema. Materials and methods A total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and four types of dermal backflow patterns (absent; distal only; proximal only; whole lower limb) were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole lower limb at 3 months (early response) and 1 year (late response) was measured. Volume difference ratios (continuous variable and binary variable with a cut-off value of zero) were compared according to the lymphoscintigraphic variables. Results The group with whole lower limb dermal backflow had a greater volume change than the other groups (p = 0.047). The group with dermal backflow in the whole lower limb OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p = 0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p = 0.016, p = 0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p = 0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p = 0.040). Conclusions Preoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.

Performance of Relative Clearance Ratio of Floating Ring Bearing for Turbocharger-Rotor System Stability

The floating ring bearing (FRB) has been widely used in the field of high-speed rotating machinery such as turbochargers, aviation engines and so on, because of its simple structure, high efficiency and low power consumption. In order to obtain the best ratio between inter-oil clearance and shaft radius of the floating ring bearing necessitates the design reference of dimensional parameters for the design of floating ring bearings. This study, based on the transfer-matrix method, developed the dynamic model of the floating ring bearing-rotor system, and, using the Runge–Kutta analysis method for floating ring bearings, the influence of oil film relative clearance ratio of floating rings on rotor system stability was analyzed and studied. The optimum clearance ratio between inner oil film and the shaft of floating ring bearings is λ = 0.01. This research can provide some theoretical support for the design of parameters and fault diagnosis of rotor floating ring bearing systems.

Persistent hypercalcemia with similar familial Hypocalciuric hypercalcemia features: a case report and literature review

Background Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the most important differential diagnosis of parathyroid hormone (PTH)-dependent hypercalcemia. The clinical features of FHH and PHPT can overlap in some cases. Therefore, these two diseases must be differentiated to prevent unnecessary parathyroidectomy. Here, we present a case that was not entirely matched with any of the known differential diagnoses of hypercalcemia. Case presentation A 19-year-old girl with no history of any disease presented with persistent hypercalcemia without any specific musculoskeletal complaint. We found persistent hypercalcemia in her routine laboratory data from 3 years ago; while no data was available during the childhood period. Her dietary calcium intake was normal. She did not mention any history of renal stone, bone fracture as well as family history of hypercalcemia. Biochemical features showed normal values of serum creatinine, high normal serum calcium (range, 10.3–11.3 mg/dL; (normal range: 8.8–10.4)), and non-suppressed PTH levels (range, 37.2–58.1 pg/mL; (normal range: 10–65)). Serum 25 OH vitamin D level at the first visit was 16.1 ng/mL that treated by vitamin D supplementation. Since then, all 25 OH vitamin D levels were in the acceptable range. After correction of vitamin D deficiency during the follow-up period the calcium creatinine clearance ratio(s) (CCCR) were calculated in the range of 0.009 to 0.014 (means below 1%). The clinical and laboratory data indicate more FHH rather than PHPT. Genetic studies were negative for the common genes associated with FHH (CASR, GNA11, and AP2S1 genes) and multiple endocrine neoplasia type1 (MEN1). On the other hand, no evidence of autoimmunity was found in her to support an autoimmune FHH-like syndrome. Hence, the case did not match completely to any diagnosis of FHH and PHPT, so we decided to follow her. Conclusion We presented a patient with FHH phenotype whose common genetic tests were negative. Further research is needed to ascertain other causes leading to similar manifestations.

Mechanistic Modeling of Placental Drug Transfer in Humans: How Do Differences in Maternal/Fetal Fraction of Unbound Drug and Placental Influx/Efflux Transfer Rates Affect Fetal Pharmacokinetics?

Background: While physiologically based pharmacokinetic (PBPK) models generally predict pharmacokinetics in pregnant women successfully, the confidence in predicting fetal pharmacokinetics is limited because many parameters affecting placental drug transfer have not been mechanistically accounted for.Objectives: The objectives of this study were to implement different maternal and fetal unbound drug fractions in a PBPK framework; to predict fetal pharmacokinetics of eight drugs in the third trimester; and to quantitatively investigate how alterations in various model parameters affect predicted fetal pharmacokinetics.Methods: The ordinary differential equations of previously developed pregnancy PBPK models for eight drugs (acyclovir, cefuroxime, diazepam, dolutegravir, emtricitabine, metronidazole, ondansetron, and raltegravir) were amended to account for different unbound drug fractions in mother and fetus. Local sensitivity analyses were conducted for various parameters relevant to placental drug transfer, including influx/efflux transfer clearances across the apical and basolateral membrane of the trophoblasts.Results: For the highly-protein bound drugs diazepam, dolutegravir and ondansetron, the lower fraction unbound in the fetus vs. mother affected predicted pharmacokinetics in the umbilical vein by ≥10%. Metronidazole displayed blood flow-limited distribution across the placenta. For all drugs, umbilical vein concentrations were highly sensitive to changes in the apical influx/efflux transfer clearance ratio. Additionally, transfer clearance across the basolateral membrane was a critical parameter for cefuroxime and ondansetron.Conclusion: In healthy pregnancies, differential protein binding characteristics in mother and fetus give rise to minor differences in maternal-fetal drug exposure. Further studies are needed to differentiate passive and active transfer processes across the apical and basolateral trophoblast membrane.

Predictive role of lymphoscintigraphy undergoing lymphovenous anastomosis in patients with lower extremity lymphedema

Background We investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema. Materials and methods A total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and dermal backflow pattern were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole leg at 3 months (early response) and 1 year (late response) was measured. Results The group with whole leg dermal backflow had a greater volume change than the other groups (p=0.047). The group with dermal backflow in the whole leg OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p=0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p=0.016, p=0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p=0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p=0.040). Conclusions Preoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.

Value of CHA2DS2-VASc score and safe contrast volume for early detection of contrast induced nephropathy after percutaneous coronary intervention

Background The CHA2DS2-VASc score is utilized to order the danger of embolization in atrial fibrillation (AF). Also it has been assessed to expect the worse clinical scenario in acute coronary syndrome patients, regardless of having AF. Therefore, the study aim was to use CHA2DS2-VASc score that has such a large area of use and the safe contrast volume – that represented by volume of the dye to creatinine clearance ratio (V/CrCl) – for contrast induced nephropathy (CIN) early detection after PCI. Patients and methods A total of 259 patients who underwent elective or primary PCI were enrolled in the study. For each patient, The CHA2DS2-VASc score and V/CrCl was evaluated. The patients in our study were divided, according to CIN development to two groups. CIN was identified as a rise in serum creatinine >0.5 mg/dl or >25% increase in baseline within48 to 72 hours after PCI. Statistical analysis: the receiver operating characteristic analysis was used to detect the best cut off values to predict CIN, and we concluded the independent predictors of CIN through multivariate logistic regression analysis. Results There was significant positive correlation between Mehran score and CHA2DS2-VASc score. Independent predictors of CIN were Mehran score, V/CrCl ratio>3.2 and CHA2DS2-VASc >3, CHF or EF <40%, hypotension, anemia, primary PCI and weight. If the patient had (CHA2DS2-VASc score>3 or V/CrCl >3.2), as a single predictor, we can predict CIN with (sensitivity 96.97%, 95% CI 0.71 to 0.82). Conclusion The Mehran score, V/CrCl ratio and CHA2DS2-VASc score are strong predictors of CIN, and we can use CHA2DS2-VASc score and safe contrast volume for early detection of CIN after PCI. FUNDunding Acknowledgement Type of funding sources: None.

Zero Balance versus Conventional Hemofiltration-Impact on Renal Function and Blood Conservation in Adult Valvular

Aim: To compare conventional ultrafiltration (CUF) with zero-balanced ultrafiltration (Z-BUF) in the patients having valvular heart surgery. Methods: This cross-sectional mono-centered retrospective study was designed. The data of total 471 patients were reviewed during March 2018 to February 2020, only 98 patients fitted in the inclusion criteria and were divided into two groups with 47(47.95%) patients received CUF, while 51 (52.04%) patients were administered with Z-BUF at the Department of Cardiovascular Surgery, King Edward Medical University, Lahore, Pakistan. Statistical analysis was done using SPSS version 25. The early postoperative clinical outcomes included, renal function as primary outcome and hemodynamics stability of the patients as secondary outcome. Results: Renal functions in terms of serum creatinine (1.1 vs. 1.3mg/dL; P < 0.010) and creatinine clearance ratio (81.51vs. 67.3mL/min; P < 0.01) were improved in the patients having Z-BUF compared with CUF. Urine output was almost double in the Z-BUF cohort compared with the CUF. The hemofiltration technique had no impact on the secondary outcomes as amount of the blood loss and number of patients required blood transfusion were similar (P > 0.05) in our cohort. Conclusion: Z-BUF appeared to be better hemofiltration method than CUF during CPB when assessed in terms of renal protection without hemodynamic status in patients undergoing valvular heart surgeries in our population. Keywords: Cardiopulmonary bypass, Ultrafiltration, Renal injury, Hemoglobin, Blood transfusion