Intravenous immunoglobulin-induced thrombocytopenia: a case report and review of the literature

Background: Intravenous immunoglobulin (IVIG), a pooled blood product acquired from multiple healthy donors, is an effective treatment for various types of autoimmune diseases, haematological disorders, and infectious diseases. Adverse haematological events such as throm-bocytopenia are rarely caused by IVIG. Objectives: To investigate the phenomenon of IVIG-induced thrombocytopenia. Materials & Methods: A case study and a review of the previous literature based on a search using MEDLINE (PubMed) and ICHUSHI (for Japanese literature) electronic databases. Results: The present case of dermatomyositis exhibited two episodes of IVIG-induced thrombocytopenia, which occurred a few days after initiating IVIG and was significant within two weeks without haemorrhagic symptoms. Spontaneous remission of thrombocytopenia was repeatedly observed. Based on a review of five cases, the underlying disorders were autoimmune bullous diseases in three of the five cases. Polyethylene glycol-treated human immunoglobulin products were used in three of the five cases. The clinical course of IVIG-induced thrombocytopenia was similar to that in our present case. Conclusion: Because of the rarity of severe haemorrhagic symptoms and spontaneous remission of IVIG-induced thrombocytopenia, discontinuation of IVIG due to thrombocytopenia is not straightforward.

Comparison of surgical morbidities between LigaSure™ and conventional techniques in inguinal or ilioinguinal lymph node dissection for skin cancer: A single center retrospective study.

Skin cancer patients with clinical nodal disease or whose positive sentinel nodes had great tumor burden remain candidates for regional lymph node dissections. Among these patients, inguinal or ilioinguinal lymph node dissection is frequently required in clinical practice, which is associated with significant postoperative morbidity-including lymphatic leakage. The aim of this retrospective study was to evaluate the efficacy of LigaSure™, an electrothermal bipolar vessel sealing system, in reducing lymphatic leakage in inguinal or ilioinguinal lymph node dissection. In total, 58 patients who received inguinal or ilioinguinal lymph node dissection (conventional group, 48; LigaSure™ group, 10) and shared similar characteristics were included in this study. Lymphatic leakage after drain removal was significantly lower in the LigaSure™ group than that in the conventional group (present ratio, 0% vs. 37%; p = 0.02). The daily lymphatic drainage volume also tended to be lower in the LigaSure™ than that in the conventional group, with significant differences on postoperative day 1 (p = 0.02). Other perioperative outcomes including the operating time, intraoperative blood loss, time to drain removal, duration of hospital stay, flap necrosis, and wound infection showed no significant differences between the two groups. The use of the LigaSure™ in inguinal or ilioinguinal lymph node dissection for the treatment of skin cancer could reduce the incidence of postoperative lymphatic leakage after drain removal.

Development of systemic lupus erythematosus after dupilumab treatment in a case of atopic dermatitis.

Dupilumab, a monoclonal antibody that specifically inhibits signal transductions by interleukin (IL)-4 and IL-13, has been used to treat T-helper (Th)2-type allergic disorders, including atopic dermatitis and asthma. We report a 21-year-old female patient with atopic dermatitis who developed systemic lupus erythematosus (SLE) unexpectedly after dupilumab treatment. Her skin lesions partially improved after dupilumab treatment; however, a part of her skin lesions on the face, nape, and upper extremities were refractory even after a 15-month period of dupilumab treatment. These dupilumab-refractory skin lesions were histopathologically diagnosed as cutaneous lupus erythematosus, moreover, subsequent phenomenons, diffuse alopecia, joint pain, lymphopaenia, hypocomplementemia, and positivities for anti-nuclear, anti-double-stranded DNA, anti-U1 ribonucleoprotein, anti-Smith, and anti-Sjögren's syndrome-related antigen A antibodies made a diagnosis of SLE. Our retrospective investigations on her serum samples indicted that these abnormalities of laboratory examinations had not appeared at the initiation of dupilumab treatment. Our case at least indicated that dupilumab was not effective in treating SLE. Moreover, inhibition of Th2-type immune responses by dupilumab may accelerate the pathogenesis of Th1-related inflammatory disorders, including SLE, as observed in our case. Our case also presented another possibility that dupilumab has no effect on the progression of underlying SLE. Because a significant relationship exists between atopic dermatitis/asthma and the risk of SLE, the utility of dupilumab should be carefully considered for each case.

A prospective, phase II study on the safety and efficacy of negative pressure closure for the stabilization of split-thickness skin graft in large or muscle-exposing defects: The NPSG study.

Several studies have demonstrated the usefulness of negative pressure closure (NPC) for the stabilization of skin grafts because it provides a uniform pressure to the graft. The results of our previous retrospective study also suggested the superiority of NPC over tie-over methods for the stabilization of split-thickness skin graft (STSG) in large or muscle-exposing defects. However, the usefulness of NPC for graft stabilization is yet to be fully established. This prospective, phase II clinical study was conducted to investigate the safety and efficacy of NPC for the stabilization of STSG in large or muscle-exposing defects. Patients who would require STSG for reconstruction of defects in the trunk and extremities other than hands and feet measuring >10 cm in the longest diameter or with muscle exposure were enrolled. NPC was applied for skin graft stabilization. Seven patients who had received wide excision of malignant tumors and resulted in muscle-exposed skin defects were included. All patients underwent meshed STSG. The mean size of the defect was 94.5 cm2 (range 63.6-164.9). The mean time from the skin graft harvesting to the NPC stabilization was 15.6 min (range 10.7-19.5). The mean survival rate of the skin graft at postoperative day 7 and 10 was 98.7% (range 97-100) and 96.5% (range 89.4-98.4), respectively. No adverse events associated with the procedure were observed. This prospective study provided further evidence of the safety and efficacy of NPC for STSG stabilization in patients with large or muscle-exposing skin defects.

Invasive and in situ lesions of squamous cell carcinoma are independent factors for postoperative surgical-site infection after outpatient skin tumors surgery: A retrospective study of 512 patients.

Surgical-site infection (SSI) is one of the major postoperative complications in surgery, which can cause significant morbidity. However, factors associated with SSI in dermatological surgery are not well understood. Here, we retrospectively investigated 512 patients who underwent outpatient surgery for skin tumors at the University of Tsukuba Hospital to analyze factors associated with postoperative SSI. The overall incidence of SSI was 28 (5.5%). Univariate logistic regression analysis revealed that SSI was significantly associated with invasive squamous cell carcinoma (iSCC), Bowen's disease (BD), actinic keratosis (AK), longer diameter of defects, presence of ulcer, reconstruction with full-thickness skin graft and local skin flaps, medical history of diabetes mellitus, and use of immunosuppressive agents. However, in the multivariate analysis only iSCC, BD, and AK retained significance. The frequencies of SSI in iSCC, BD, and AK were 22% (13/58 patients), 15.6% (5/32), and 25% (2/8), respectively; however, the frequency of other non-SCC tumors was only 1.9% (8/414). χ2 -Tests revealed that the frequency of SSI in iSCC, BD, and AK were all significantly higher than in non-SCC tumors, with the frequencies being more than eight times higher. These results suggest that invasive and in situ lesions of SCC are independent risk factors of SSI development after outpatient skin surgery.

The Platelet Count Can Predict In-hospital Death in HIV-negative Smear-positive Pulmonary Tuberculosis Inpatients.

Objective This retrospective cohort study investigated whether the three components of the blood cell count have prognostic implications in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis. Methods We reviewed patients who were treated by the isoniazid, rifampicin, pyrazinamide, and ethambutol regimen or by the isoniazid, rifampicin, and ethambutol regimen. The association between the patient data on admission and the survival outcome was evaluated. Results We reviewed 367 consecutive patients (male, 60.5%) with a median age of 72 [interquartile range (IQR), 54-82] years. While the white blood cell count did not differ between the two groups, (discharged alive: 7,000/µL; IQR, 5,500-9,300; died in hospital: 7,200/µL; IQR, 5,600-9,400; p=0.797), hemoglobin level (discharged alive: 11.5 g/dL; IQR, 10.0-13.1; died in hospital: 9.9 g/dL; IQR, 8.6-11.3; p<0.001) and the platelet count (discharged alive: 275,000/µL; IQR, 206,000-345,000; died in hospital: 149,000/µL; IQR, 93,000-236,000; p<0.001) were lower in patients who died in hospital. After dividing patients into hemoglobin- and platelet-based quantiles, the lower quantile class tended to show poorer survival (log-rank test for trend p<0.001 for both). A multi-variable Cox proportional hazards model revealed that hazard ratio for in-hospital death for every 1,000/µL increase of platelet count was 0.997 (95%CI, 0.995-0.999; p=0.010); the hazard ratio for the hemoglobin level was not significant. Conclusion A low platelet count was clearly related to a poor life prognosis in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis.

Factors for Predicting Outcomes among Non-HIV Patients with Pulmonary Tuberculosis.

Objective Onodera's Prognostic Nutritional Index (PNI), determined as "10× albumin (g/dL) + 0.005× lymphocyte count (/µL)," was originally designed to determine the risk of complications following gastrointestinal surgery. This single-center, retrospective observational study was designed to investigate whether or not the PNI can predict the treatment outcome. Methods We consecutively reviewed HIV-negative pulmonary tuberculosis adults in an isolation ward. Most patients were being treated with standard three- or four-drug regimens. Patients were discharged after consecutive negative smears/cultures were confirmed. The risk of all-cause death was assessed using a multivariable Cox proportional hazard model and a log-rank trend test. Results During the observation period, we observed 371 consecutive patients with a median age of 72 (interquartile range [IQR]: 54-82) years. In our cohort, 295 (79.5%) patients were discharged alive, and 76 (20.5%) died in-hospital. Patients who died in-hospital had a lower PNI [median 21.2 (IQR: 18.5-25.9)] than those who were discharged alive [median 35.1 (IQR: 28.0-43.3); p<0.001]. The area under the receiver operating characteristic curve was 0.87. After dividing the patients based on the baseline PNI quartile, those patients with a lower PNI showed a poorer survival than those with a higher PNI (log-rank trend p<0.001). After adjusting for other baseline variables, the baseline PNI was still associated with in-hospital death with a hazard ratio of 0.86 (95% confidence interval: 0.82-0.91, p<0.001). Conclusion Our results showed that a low PNI was clearly related to a poor survival prognosis in smear-positive HIV-negative pulmonary tuberculosis inpatients.

Design of Enzyme-Encapsulated Protein Containers by In Vivo Crystal Engineering.

Crystalline protein assemblies of polyhedra crystal (PhC) can be utilized as solid enzyme containers for long-term storage of enzymes with retention of their enzymatic activity. The enzymes can be released from the crystals at the optimum pH for the enzymatic activity by dissolution of the crystals using in vivo crystal engineering.