Gain of function mutation in K(ATP) channels and resulting upregulation of coupling conductance are partners in crime in the impairment of Ca2+ oscillations in pancreatic ß-cells.

Gain of function mutations in the pore forming Kir6 subunits of the ATP sensitive K+ channels (K(ATP) channels) of pancreatic ß-cells are the major cause of neonatal diabetes in humans. In this study, we show that in insulin secreting mouse ß-cell lines, gain of function mutations in Kir6.1 result in a significant connexin36 (Cx36) overexpression, which form gap junctional connections and mediate electrical coupling between ß-cells within pancreatic islets. Using computational modeling, we show that upregulation in Cx36 might play a functional role in the impairment of glucose stimulated Ca2+ oscillations in a cluster of ß-cells with Kir6.1 gain of function mutations in their K(ATP) channels (GoF-K(ATP) channels). Our results show that without an increase in Cx36 expression, a gain of function mutation in Kir6.1 might not be sufficient to diminish glucose stimulated Ca2+ oscillations in a ß-cell cluster. We also show that a reduced Cx36 expression, which leads to loss of coordination in a wild-type ß-cell cluster, restores coordinated Ca2+ oscillations in a ß-cell cluster with GoF-K(ATP) channels. Our results indicate that in a heterogenous ß-cell cluster with GoF-K(ATP) channels, there is an inverted u-shaped nonmonotonic relation between the cluster activity and Cx36 expression. These results show that in a neonatal diabetic ß-cell model, gain of function mutations in the Kir6.1 cause Cx36 overexpression, which aggravates the impairment of glucose stimulated Ca2+ oscillations.

Mortality Factors in Crush Syndrome.

BACKGROUND: Crush Syndrome is a major cause of morbidity and mortality following large-scale catastrophic earthquakes. Since there are no randomized controlled studies on Crush Syndrome, knowledge on this subject is limited to expert experience. The primary objective is to analyze the epidemiological and demographic characteristics, clinical outcomes, and mortality factors of earthquake victims after the Pazarcik and Elbistan earthquakes on February 6, 2023. METHODS: This cross-sectional and observational retrospective study evaluated 610 earthquake victims who presented to our center between February 6 and April 30, 2023. Among these patients, 128 with Crush Syndrome were included in the study. Patient information was gathered from hospital records during their stay and from national registries upon referral. The primary outcome was to identify risk factors for mortality. Demographic and laboratory data were analyzed by acute kidney injury (AKI) stages; mortality-affecting factors were identified through regression analysis. RESULTS: Of the 128 Crush Syndrome patients (100 adults, 28 children), 64 were female. The AKI rate was 32.8%. Among patients with AKI, the frequency of hemodialysis requirement was 69%, and the mortality rate was 14.2%. The overall mortality rate for patients with Crush Syndrome was 4.6%, compared to 3.9% (19/482) in earthquake victims without Crush Syndrome (p=0.705). Notably, low systolic blood pressure at admission was the only factor significantly affecting mortality in Crush Syndrome patients (Hazard Ratio [HR]: 1.088, p=0.021, 95% Confidence Interval [CI]). CONCLUSION: Our study highlights low systolic blood pressure upon admission as a significant risk factor for increased mortality in Crush Syndrome patients. This finding may contribute to the literature by emphasizing the importance of monitoring blood pressure under rubble and administering more aggressive fluid therapy to patients with low systolic blood pressure.

Diagnostic clues in a stem cell transplant patient manifested with chronic central nervous system GVHD and IRIS.

Transplant physicians should be aware of the immune deviation-related clinical conditions as allogeneic hematopoietic stem cell transplantation is widely used for the treatment of patients with malignant and non-malignant disorders. Neurological manifestations and graft-versus-host disease (GVHD) may commonly develop in transplant recipients. However, overlapping clinical immunological conditions may lead to diagnostic challenges. Herein, we discussed the differential diagnosis of a patient with immune reconstitution inflammatory syndrome (IRIS) developing on the basis of chronic GVHD.

Retrospective evaluation of quality of life in patients undergoing sacroiliac joint denervation with simplicity.

OBJECTIVES: The sacroiliac joint (SIJ) is the third most common cause of low back pain. The treatment of SIJ-induced pain is often conservative. When conservative treatments fail, interventional treatment methods, such as intra-articular injection or radiofrequency (RF) denervation are applied. Recently, in addition to the success of this interventional treatment applied, increased patient satisfaction and quality of life after treatment have also gained importance. The aim of this retrospective study was to evaluate pain management and improvement in the quality of life in patients with SIJ pain who underwent RF denervation with the simplicity probe. METHODS: The files of patients with SIJ degeneration on Ferguson X-ray, who underwent diagnostic intra-articular block for SIJ and had more than 50% reduction in pain were screened, and 38 cases in which simplicity RF neurotomy was applied were identified. The age, sex, and numerical rating scale (NRS) and short form (SF)-36 scores of the remaining 30 patients were recorded before and at 6 months after the procedure. RESULTS: There was a statistically significant decrease in NRS between the pre-procedure and post-procedure (6-month) values. The decrease in NRS did not significantly differ according to sex. A statistically significant improvement in all the domains of SF-36 in the post-procedure period compared to the pre-procedure period. There was no significant sex-related difference in the improvement of the SF-36 domains, except for the emotional role functioning domain, for which the scores were significantly higher in women than in men. CONCLUSION: In patients with SIJ pain who positively respond to steroid injection, the application of Simplicity III achieves long-term pain management and increases patient comfort and satisfaction pain without any complications.

[Two Case of Rhino-Orbito-Cerebral Mucormicosis Developed After COVID-19 Infection]. / COVID-19 Enfeksiyonu Sonrasi Gelisen Iki Rino-Orbito-Serebral Mukormikoz Olgusu.

Coronavirus 2019 (COVID-19) infection causes excessive cytokine response and a decrease in cellular immune response and this increases susceptibility to fungal co-infections. Mucormycosis is a rare, lifethreatening invasive fungal infection. In this report, two cases who developed rhino-orbito-cerebral mucormycosis shortly after having COVID-19 infection were presented. The first case was a 68-year old woman who admitted to our clinic with orbital cellulitis in her left eye and had a known diagnosis of asthma and rheumatoid arthritis. She was diagnosed with COVID-19 pneumonia 40 days ago, stayed in the intensive care unit for a long time, and received pulse steroid (1000 mg methylprednisolone), interleukin-1 (IL-1) inhibitor (anakinra) and broad-spectrum antibiotic treatments together with antiviral therapy during this period. The second case was a 63-year-old male patient with known diabetes mellitus, hypertension and retinitis pigmentosa, with a history of hospitalization in the intensive care unit due to COVID-19 pneumonia 20 days ago and received pulse steroid therapy during this period. He admitted to our clinic with the complaints of droopy right eyelid, swelling, nausea and vomiting. In both cases, paranasal sinus tomography findings were consistent with invasive sinusitis. Functional endoscopic sinus surgery was performed immediately in less than 16 hours from the first admission in both cases. Histopathological examination of the both cases revealed results consistent with mucormycosis. Mucorales spp. was isolated in sinus tissue culture of the second case taken during the operation. Both of the patients received liposomal amphotericin B. First case died on the 19th day of the treatment. Second case was discharged with full recovery after nine weeks of treatment. The suppression of cellular immunity during the COVID-19 infection, and the use of steroids and interleukin inhibitors in the treatment of severe cases may increase secondary invasive fungal infections. Therefore, clinicians should more frequently consider possible fungal infections in patients with COVID-19.