Immunotherapy of prolactinoma with a T helper 1 activator adjuvant and autoantigens: a case report

OBJECTIVE: To date, efforts to reliably manipulate the immune system to promote tumor regression in the brain have been disappointing. We report a unique experience of successful immunotherapy to treat a pituitary macroprolactinoma. METHODS: A 31-year-old woman with an established history of pituitary macroprolactinoma who had undergone tumor resection followed by radiation was admitted to our clinic. The diagnosis had been made due to the patient's symptoms, a serum prolactin (PRL) level of 29,600 mIU/l, a brain MRI revealing a 23 x 19 x 18 mm pituitary mass and a positive PRL immunohistochemistry of the mass. Six months following surgery, she reexperienced headache, excessive sweating and a serum PRL concentration of 2,960 mIU/l despite receiving 30 mg/day bromocriptine. Brain MRI revealed a pituitary mass (3 x 6 x 8 mm) compatible with a pituitary adenoma. Twenty micrograms per milliliter of G2 (as a T helper 1 activator adjuvant) was inoculated intradermally once per week for 24 consecutive weeks (each injection contained 10 mug of G2). The autoantigens were inoculated at the same time with G2. RESULTS: After immunotherapy, serum PRL concentration decreased to 82 mIU/l, the patient's symptoms disappeared, skin thickness increased to normal and bromocriptine dosage was tapered to 20 mg per week. A follow-up brain MRI revealed almost complete disappearance of the tumor. The patient does not complain of any problems at 1-year follow-up. CONCLUSION: Activation of both nonspecific (natural killer cells) and specific (cytotoxic T lymphocytes) immunity in relation to the T helper 1 cytokine network is a promising strategy for the treatment of tumors of the central nervous system in humans, especially pituitary macroprolactinomas.     

Transcutaneous Electrical Nerve Stimulation at the Acupuncture Points to Relieve Pain of Patients Under Mechanical Ventilation: A Randomized Controlled Study

Background and objective

Electrical stimulation and acupuncture points as nonpharmacological methods have been the focus of pain reduction in different patients. This study is aimed at determining the effects of transcutaneous electrical nerve stimulation (TENS) on the acupuncture points of pain in patients under mechanical ventilators.

Comparative pathogenicity of opportunistic black yeasts in Aureobasidium

Aureobasidium pullulans and A. melanogenum are black‐yeast‐like surface colonisers and are commonly encountered as contaminants in the hospital. The species are able to produce melanin which play a role in protection against environmental stress and irradiation. Aureobasidium melanogenum shows higher frequency in opportunistic infections compared to A. pullulans. Comparative pathogenicity of opportunistic black yeasts between Aureobasidium pullulans and A. melanogenum to explain the observed differences in frequency in infection. Degrees of melanisation and thermotolerance were measured, and virulence of strains from different sources was examined in Galleria mellonela and murine infection models. Aureobasidium melanogenum responds with increased melanisation to temperature stress and generally survives at 37°C, A. pullulans on average scored less on these parameters. In the murine model, differences between species were not significant, but the melanised A. melanogenum group showed the highest virulence. This result was not reproducible in Galleria mellonella larvae at 25°C. The A. melanogenum black group showed higher pathogenicity in murine model, indicating that the combination of melanisation and thermotolerance rather than species affiliation is instrumental. Galleria larvae did not survive very well at 37°C, and hence, this model is judged insufficient to detect the small virulence differences observed in Aureobasidium.     

On the immunological limitations of hibernation and synthetic torpor as a supporting technique for astronauts’ radioprotection in deep space missions

Although human hibernation has been introduced as an effective technique in space exploration,there are concerns regarding the intrinsic risks of the approach(i.e.,synthetic torpor)and other factors involved in this procedure.Besides concerns about the brain changes and the state of consciousness during hibernation,an"Achilles heel"of the hibernation is the negative impact of torpor on factors such as the number of circulating leukocytes,complement levels,response to lipopolysaccharides,phagocytotic capacity,cytokine production,lymphocyte proliferation,and antibody production.Moreover,increased virulence of bacteria in deep space can significantly increase the risk of infection.The increased infection risk during long-term space missions with the combined effects of radiation and microgravity affect the astronauts’immune system.With these additional immune system stressors,torpor-induced extraimmunosuppression can be potentially life threatening for astronauts.     

Moderate‐intensity exercise training ameliorates the diabetes‐suppressed spermatogenesis and improves sperm parameters: Insole and simultaneous with insulin

The current study was conducted to investigate the ameliorative effect of moderate‐intensity exercise training insole and simultaneous with insulin on diabetes (DM)‐induced pathogenesis at the testicular tissue and sperm level. For this purpose, 36 mature male Wistar rats were divided into six groups, including sedentary control (Con), exercise training (EX), sedentary experimental DM‐induced (SDM), exercise training + DM‐induced (DM + EX), insulin‐treated sedentary DM‐induced (DM + INS) and exercise training and insulin‐treated DM‐induced (DM + INS + EX) groups. Following DM induction, the 6‐week exercise training intervention (30 min of moderate‐intensity running on a treadmill, once daily [5 days/week]) was considered in EX groups. The tubular differentiation (TDI) and spermiogenesis (SPI) indices, testicular total antioxidant capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPX) contents, serum testosterone and insulin levels, the apoptosis ratio and sperm parameters were assessed. The exercise in sole (EX) and simultaneous forms with INS (DM + INS + EX group) ameliorated the DM‐suppressed spermatogenesis and spermiogenesis indices, up‐regulated the serum testosterone and insulin levels, enhanced testicular SOD content, inhibited the apoptosis and improved almost all sperm parameters. In conclusion, exercise training, when simultaneously considered with insulin, fairly boosts the insulin‐induced impacts, including the up‐regulated testicular endocrine and antioxidant status, spermatogenesis and sperm quality.     

Definition of a Novel Proximal Femur Classification in the Sagittal Plane According to the Femur Morphometric Analysis

BackgroundStudies on prosthesis positioning and implant design in total hip arthroplasty (THA) have generally focused on the anatomy of the proximal femur in the coronal plane. The aim of this study was to investigate the proximal femur morphology in the sagittal plane to provide better positioning of the femoral component in THA and contribute to the determination of proximal femur morphology through possible outcomes that can be shown also by considering the sagittal plane in the selection and design of the femoral component.MethodsComputerized tomography scans were obtained from 270 femoral bones belonging to adult skeletons, followed by 3D reconstruction using Leonardo Dr/Dsa Va30a software (Siemens, Erlangen, Germany) and measurements. Canal widths were measured in the coronal and sagittal planes at the lesser trochanter (LT) level, at 20 millimeters proximal to the LT(LT+20) and at various levels distal to the lesser trochanter in 25 mm jumps up to 200 mm from the lesser trochanter.ResultsThe average width was wider at the level of the lesser trochanter and all points distal to it in the sagittal plane compared to the coronal plane except LT?200 mm. At each levels from LT?25 to LT?175, the differences were statistically significant (P < .05). The ratio of the femoral width at the lesser trochanter level to the width 50 mm distal to the LT was stated as the most prevalent one, and a novel classification in the sagittal plane was developed in accordance with these findings.ConclusionA novel and simple classification in the sagittal plane was developed based on the findings of this study, and this classification may improve the accuracy, validity, and reliability of femoral stem fixation in total hip arthroplasty.     

Conversion Total Knee Arthroplasty Needs Its Own Diagnosis-Related Group Code

BackgroundConversion from a prior knee procedure has been demonstrated to require greater operative times and resources, but still lacks a separate procedural or facility code from primary total knee arthroplasty (TKA). The purpose of this study is to determine differences in facility costs between patients who underwent primary TKA and those who underwent conversion TKA.MethodsWe retrospectively reviewed a consecutive series of patients undergoing primary TKA at 2 hospitals from 2015 to 2017, comparing itemized facility costs between primary and conversion TKA patients. A multivariate regression analysis was performed to identify independent risk factors for increased facility costs, the need for additional implants, length of stay, and discharge disposition.ResultsOf 2447 TKA procedures, 678 (27.7%) underwent conversion TKA, which was associated with greater implant costs ($3931.47 vs $2864.67, P = .0120) and total facility costs in a multivariate regression ($94.30 increase, P = .0316). When controlling for confounding variables, patients with a prior ligament reconstruction ($402 increase, P = .0002) and prior open reduction and internal fixation ($847 increase, P = .0020) had higher costs and were more likely to require stemmed implants (P < .05). There was an increase in TKA implant cost by $538 in patients with implants from a prior procedure (P < .0001).ConclusionConversion TKA is associated with greater implant and inpatient facility costs than primary TKA, particularly those who had a history of an open knee procedure. A separate diagnosis-related group should be created for conversion TKA given the increased cost and complexity of these procedures compared to primary TKA.     

Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection: The Rate and Reason for the Attrition After the First Stage

BackgroundTwo-stage exchange arthroplasty remains a popular surgical treatment for patients with chronic periprosthetic joint infection (PJI). Patients who do not receive reimplantation were largely overlooked in the current literature. We aimed at investigating the clinical outcomes of these patients.MethodsOur institutional PJI database was retrospectively reviewed to identify 616 patients (237 hips, 379 knees) who were treated with an intended 2-stage exchange. Of them, 111 (18%) did not receive reimplantation within a minimum follow-up of 1 year. Chart review and targeted interviews were performed to elucidate the cause of attrition. Patients were considered to have failed treatment in the absence of reimplantation if they remained medically unfit for reimplantation, underwent a salvage procedure, or died during the study period.ResultsOf the 111 patients without reimplantation, 29 (26.1%) did well with their retained spacer and were unwilling to proceed with reimplantation, 23 (20.7%) underwent salvage procedures, and the remaining 59 (53.2%) were considered medically unfit for reimplantation, with 34 of them dying within 1 year of initial spacer insertion. The overall success rate for 2-stage exchange cohort at 2 years was 65.7% when treatment failure without reimplantation was taken into account. Several factors associated with increased risk of treatment failure without reimplantation were identified using a multivariate regression model.ConclusionAlmost 1 in 5 patients may never receive the intended reimplantation. Among many reasons for attrition, mortality appears to be a relatively common event. The current definition of treatment success does not take into account the attrition group and thus inflates the relative success of 2-stage exchange arthroplasty.     

A novel c.240_241insGG mutation in NDP gene in a family with Norrie disease

Background

Norrie disease (ND) is a rare, X‐linked recessive disorder with the main characteristic of early childhood blindness. The aim of the present study was to identify the genetic cause of the disease and the phenotypic characteristics of the patients in an Iranian family with four affected males with ND.

Methods

Norrie disease pseudoglioma (NDP) gene was sequenced and clinical examination was performed on patients.

Results

A GG dinucleotide insertion in exon 3 (c.240_241insGG) of NDP was detected in all patients. The mutation caused a frameshift and an early stop codon (p.Phe81Glyfs*23).

Conclusions

A novel mutation was found in the NDP gene in the affected males of the family. As the mutation was absent in the normal male members of the family, it should be the genetic cause of the disease.