BACKGROUND
Primary ovarian insufficiency (POI) is characterized by marked heterogeneity, but with a significant genetic contribution. Identifying exact causative genes has been challenging, with many discoveries not replicated. It is timely to take stock of the field, outlining the progress made, framing the controversies and anticipating future directions in elucidating the genetics of POI.

/pdf/genetics-of-primary-ovarian-insufficiency-new-developments-29kolr25o8.pdf

Genetics of primary ovarian insufficiency: new developments and opportunities

https://www.onlinelibrary.wiley.com/doi/pdf/10.1016/j.orthres.2004.08.010

Less systemic cytokine response in patients following microendoscopic versus open lumbar discectomy

Febrile temperatures commonly are seen after total knee arthroplasty, but their source and importance are unclear. The goal of the current study was to determine whether such fevers are part of the normal physiologic response to surgery mediated by inflammatory cytokines. In 20 patients who had total knee arthroplasty, serum and wound drain fluid samples were collected preoperatively and at 1, 6, 24, and 48 hours postoperatively; oral temperatures were measured postoperatively every 4 hours for 3 days. Concentrations of interleukin 1beta, interleukin 6, and tumor necrosis factor alpha in the samples were measured via enzyme-linked immunosorbent assays and compared in patients who did and did not have fevers develop (>or=38.5 degrees C). Gender, age, operative time, amount of blood loss or drain output, anesthesia type, drop in hematocrit, and transfusion administration were not associated with fever. Significant increases were seen postoperatively in drain fluid concentrations of interleukin 1beta and interleukin 6 and in serum concentrations of interleukin 6. Patients who were febrile had significantly higher drain and serum interleukin 6 concentrations than patients who were afebrile. These findings suggest that fevers seen after total knee arthroplasty are at least partly the result of surgical site inflammation and subsequent local and systemic release of the endogenous pyrogen interleukin 6.

Postoperative fever after total knee arthroplasty: the role of cytokines.

Local and Systemic Release of Cytokines, Nerve Growth Factor, Prostaglandin E2, and Substance P in Incisional Wounds and Serum Following Cesarean Delivery

Although reinfusion of salvaged shed blood has become popular in major orthopaedic procedures, this blood saving technique is still controversial. In an effort to assess the functional and metabolic status of shed blood erythrocytes and the impact of postoperative shed blood reinfusion on allogenic blood requirements and patient’s blood parameters, analyses of perioperative blood samples were performed in 28 consecutive orthopaedic patients undergoing spinal fusion, in which postoperative shed blood was collected and reinfused with the ConstaVac CBC II device. In comparison with a previous series of 31 patients, this procedure reduced allogenic blood requirements by almost 30% (P < 0.05), without any increase in postoperative complications. Postoperative shed blood presented lower haematological values and higher plasma-free haemoglobin (PFHB) levels than preoperative blood, without any disturbance in morphology, median corpuscular fragility (MCF) or erythrocyte adenosine triphosphate (ATP) and diphosphoglycerate (DPG) content. Serum concentrations of enzymes – glutamate-oxalacetate aminotransferase (GOT), glutamate-piruvate aminotransferase (GPT), creatine kinase (CK), lactate dehydrogenase (LDH) – and inflammatory cytokines (IL-1β, IL-6) were elevated in shed blood. After reinfusion, there was no alteration in coagulation parameters or cytokine levels. Serum levels of some enzymes increased at the end of surgery and remained elevated at postoperative day 2 (CK) or 7 (GOT, LDH), with a higher increase if postoperative autotransfusion was used as a blood saving method. Therefore, caution should be taken when these serum enzyme levels are used for diagnosis. In conclusion, salvaged shed blood in orthopaedic procedures of the spine seems to be an excellent source of red cells which are not significantly damaged, keeping a normal functional and metabolic status, and reduces allogenic blood requirements without significant side effects.

/pdf/postoperative-blood-salvage-and-reinfusion-in-spinal-surgery-og9u0zgesw.pdf

Postoperative blood salvage and reinfusion in spinal surgery: blood quality, effectiveness and impact on patient blood parameters.

To investigate cytokine and coagulation/fibrinolysis characteristics in blood retrieved from wounds using an autotransfusion system, and to compare the cytokine pattern in the retrieved blood with those in the systemic circulation and in the initial portion of drainage blood from the wound. Prospective controlled clinical study. The postoperative ward of a University hospital. Blood retrieval was performed over a period of 4–6 h on patients who had just undergone arthroplasty (nine hips, one knee). In five other cases involving hip arthroplasties, the initial portion of drainage blood was studied. Coagulation/fibrinolysis parameters were analyzed in blood retrieved using the Stryker Consta Vac system. Concentrations of tumor necrosis factor α (TNF), interleukin-1 β (IL-1) and interleukin-6 (IL-6) were analyzed in the retrieved blood, in the systemic circulation of the patients at the beginning and at the end of blood retrieval and in the initial portion of drainage blood from the surgical area. In the retrieved blood, the activities of thrombin, kallikrein and plasmin were increased, antithrombin and free protein S were decreased, and in all samples IL-6 was >1000 pg/ml. Postoperative plasma concentrations of IL-6 rose from a median value of 0 to 116 pg/ml (p<0.01). Four patients had circulating TNF concentrations (range: <15–50 pg/ml). Plasma IL-1 was not detected. TNF and IL-1 were detected in all samples of initial blood from the surgical area and IL-6 in one sample. Hypercoagulability and high concentrations of IL-6 were present in the retrieved blood. The cytokine pattern in the initial portion of blood from the surgical area differed from those in the retrieved blood and in the systemic circulation.

Cytokine and coagulation characteristics of retrieved blood after arthroplasty

Local and systemic immune and haemostatic responses were studied in 10 patients, aged 57-78 years, undergoing elective hip arthroplasty. Cytokines, soluble cytokine receptors, interleukin-1 receptor antagonist, soluble adhesion molecules, antithrombin, fibrin, soluble and fibrin D-dimer were analysed in wound drainage blood and in blood taken from the systemic circulation for up to 24 h post-operatively. Wound drainage blood concentrations of cytokines, interleukin-1 receptor antagonist and soluble cytokine receptors were increased compared with those in the systemic circulation except for the soluble interleukin-6 receptor. In wound drainage blood, soluble tumour necrosis factor receptors (P < 0.05), interleukin-1 receptor antagonist (P < 0.05) and interleukin-6 (P < 0.05-< 0.01) increased during the study period. In blood from the systemic circulation interleukin-6 increased (P < 0.05) while the soluble interleukin-6 receptor decreased (P < 0.05) compared with pre-operative values. Concentrations of soluble adhesion molecules did not change. Wound drainage blood showed marked hypercoagulation. After hip arthroplasty pro-inflammatory cytokines and their inhibitors were mainly confined to the local trauma site. A predominance for inhibitors was noted.

Local vs. systemic immune and haemostatic response to hip arthroplasty

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Cytokine and coagulation characteristics of retrieved blood after arthroplasty

Local vs. systemic immune and haemostatic response to hip arthroplasty