Does Systemic Hematological Therapy Influence the Course of Paraproteinemic Keratopathy?

The purpose of this article is to evaluate the course of paraproteinemic keratopathy (PPK) in patients undergoing systemic therapy for the underlying hematological disease. Baseline and follow-up examinations included hematological work-up, best-corrected visual acuity, slit-lamp biomicroscopy, and in vivo confocal laser scanning microscopy (IVCM). We included 22 patients with bilateral PPK (aged 68 ± 10.4 years, 11 males). Ten patients with multiple myeloma (MM) underwent on-label systemic therapy. During follow-up, we observed a regression of corneal opacities in three patients under slit-lamp examination and under IVCM, while PPK remained unchanged in seven patients. In three patients with monoclonal gammopathy of ocular significance (MGOS), systemic therapy was initiated off-label to reduce the serum paraprotein load before penetrating keratoplasty (PKP). These patients showed no signs of PPK recurrence for up to 24 months after PKP. In one patient without systemic therapy, a recurrence in corneal grafts occurred within 12 months of PKP. In eight patients without systemic therapy, PPK remained stable. In conclusion, systemic therapy for MM patients reduced corneal opacity in 30% of treated patients. Furthermore, systemic therapy performed before PKP in patients without conventional systemic therapy indication (MGOS) likely postpones PPK recurrence in the corneal graft.

Prevalence of Herpes Simplex and Varicella-Zoster Virus DNA in Corneal Grafts Is Higher than Expected.

PURPOSE: (1) To determine the prevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV) DNA in donor corneas; (2) To evaluate the clinical outcome of the grafts with viral DNA and to compare donors with and without viral DNA. METHODS: We analyzed data from all donors and recipients who underwent penetrating keratoplasty (PK) or Descemet membrane endothelial keratoplasty (DMEK) between September 2022 and March 2023. Donor corneoscleral rims and excised recipients' corneal buttons were tested for the presence of HSV-1, HSV-2, VZV, and CMV DNA by polymerase chain reaction (PCR). The results were known 2-3 days after the surgery. We closely followed up on patients whose grafts tested positive for viral DNA. We compared the medical histories of donors with and without viral DNA. RESULTS: We included 85 corneas from 67 donors. Seven (8.2%) donor corneas tested positive for HSV-1 (n = 3) or VZV (n = 4) DNA. We did not detect any HSV-2 or CMV DNA. In the postoperative follow-up of patients with positive PCR, a graft failure was observed in one and infections in two eyes. Re-operation was necessary in three of these cases (42.9%). Patients without herpes DNA in the donor cornea needed reoperation in 7.7% of the cases. Cultural duration, the cause of the donor's death, and the death-to-explantation interval did not differ significantly between donors with and without viral DNA. Additionally, 3 of the 7 (42.9%) donors with positive PCR were in a septic status at the time of death, compared to 21 of the 78 (26.9%) donors with negative PCR (p = 0.52). CONCLUSIONS: The prevalence of herpes DNA in the donor corneas was 8.2% and thus higher than previously reported. We did not notice any evidence for a donor-to-host transmission, but a higher rate of postoperative complications in recipients of the grafts with viral DNA. The donors with and without herpetic DNA did not differ significantly regarding systemic diagnoses or cultural conditions, but sepsis was more frequent in the group with viral DNA.

Hospital Work Conditions and the Mediation Role of Burnout: Residents and Practicing Physicians Reporting Adverse Events.

Background: "Patient Safety" in everyday practices is a target of healthcare leaders, and adverse events reported by healthcare providers directly reflect patient safety in the health system. Recognising how residents and practising physicians rate adverse events concerning their work conditions and burnout must be explored. Objective: This study aims to explore the mediation effect of burnout dimensions (emotional exhaustion and burnout-interpersonal disengagement) between the effects of work conditions on perceived patient safety by exploring the adverse events that residents and practising physicians reported. Methods: A quantitative and cross-sectional study collected data from 249 residents and practising physicians in a huge teaching hospital and primary health care centre (PHC) in the Eastern Province of Saudi Arabia. Hayes Macro regression analysis was employed to evaluate the multiple mediation effect of burnout dimensions, with 5000 bootstrapping and a confidence interval (CI) of 95% for statistical inference and p≤0.05 for the significance level. Results: Leadership support (B= 0.39, t= 6.24, p<0.001) and physician engagement (B=0.43, t=6.50, p<0.001) were associated with a decreased rate of adverse events to patient safety, whereas workload (B=-0.23, t=-3.73, p<0.001) was negatively associated with an increased rate of adverse events. Burnout was shown to mediate the relationship between the effects of physician's leadership support (R2=0.26, F=27.50, p<0.001), work engagement (R2=0.25, F=27.07, p<0.001) and workload (R2=0.23, F=24.23, p<0.001) on the rate of adverse events. Conclusion: This study provides insights into burnout dimensions and their consequences on patient safety indicators (ie, adverse events). Work conditions (ie, leadership support, physician engagement, and workload) directly affect the rate of adverse events and indirectly through mediators like burnout-emotional exhaustion and burnout-interpersonal disengagement.

Prevalence of corneal findings and their interrelation with hematological findings in monoclonal gammopathy.

PURPOSE: To determine prevalence of paraproteinemic keratopathy (PPK) among patients with monoclonal gammopathy (MG). To evaluate interrelation between corneal and hematological parameters in patients with PPK. METHODS: Fifty-one patients with monoclonal gammopathy of undetermined significance (n = 19), smoldering multiple myeloma (n = 5) or multiple myeloma (n = 27) were prospectively included in this study. Best-corrected visual acuity, slit-lamp biomicroscopy, Scheimpflug tomography, in-vivo confocal laser scanning microscopy, optical coherence tomography and complete hematological workup were assessed. RESULTS: We identified n = 19 patients with bilateral corneal opacities compatible with PPK. PPK was newly diagnosed in 13 (29%) of 45 patients with a primary hematological diagnosis and in n = 6 patients without previous hematological diagnosis. The most common form was a discreet stromal flake-like PPK (n = 14 of 19). The median level of M-protein (p = 0.59), IgA (p = 0.53), IgG (p = 0.79) and IgM (p = 0.59) did not differ significantly between the patients with and without PPK. The median level of the FLC κ in serum of patients with kappa-restricted plasma cell dyscrasia was 209 mg/l in patients with PPK compared to 38.1 mg/l in patients without PPK (p = 0.18). Median level of FLC lambda in serum of patients with lambda-restricted plasma cell dyscrasia was lower in patients with PPK compared to patients without PPK (p = 0.02). CONCLUSION: The PPK was mostly discreet, but its prevalence (29%) was higher than expected. Median level of the monoclonal paraprotein was not significantly higher in patients with PPK compared to patients without PPK. Our results suggest a lack of correlation between morphology and severity of the ocular findings and severity of the monoclonal gammopathy. TRIAL REGISTRATION: German Clinical Trial Register: DRKS00023893.

Monoclonal gammopathy of ocular significance (MGOS) - a short survey of corneal manifestations and treatment outcomes.

Monoclonal gammopathy of ocular significance (MGOS) is a rare subset of monoclonal gammopathy of clinical significance occurring secondary to plasma cell disorders and causing ocular manifestations. We identified 23 patients with paraproteinemic keratopathy (PPK) in the setting of monoclonal gammopathy of unknown significance (MGUS, 10), smoldering multiple myeloma (SMM, 3) or multiple myeloma (MM, 10). Many of these patients with PPK (11/23) presented decreased vision. All patients with MM and 40% of those with other diagnoses such as SMM and MGUS received systemic therapy with or without autologous stem cell transplantation. Four eyes of four patients were treated by penetrating keratoplasty. In most cases, neither ocular nor hematologic treatment afforded a durable improvement in the visual acuity (recurrence after a median of 11 months), despite initial responses. Further studies will be required to determine the optimal strategy to treat and prevent the relapse of ocular symptoms in patients with PPK.

Cardiac Inotropic Effect of Long-Term Administration of Oral Thymoquinone.

BACK GROUND: Long-term administration of Nigella sativa showed cardiac hypertrophic and positive inotropic effects. Thymoquinone (TQ) is an active ingredient in Nigella sativa. Therefore, we aimed to test the cardiac effects of long-term TQ administration. MATERIALS AND METHODS: Twenty adult Wistar rats weighing (150-250 g) were divided into two groups: control and TQ. A TQ-olive oil solution was administered orally to the TQ group (dose 10 mg/kg) for two months. An equivalent volume of olive oil was given to the control group. Langendorff isolated hearts were studied. Peak tension, time to peak tension, half relaxation time, and myocardial flow rate were determined. Heart and left ventricle weights and ratios were recorded. RESULTS: The TQ group exhibited significantly higher peak tension than the control group. There were no significant differences between the two groups in time to peak tension, half relaxation time, and myocardial flow rate. Likewise, there were no signs of cardiac hypertrophy. CONCLUSIONS: Long-term administration of oral TQ induced a positive inotropic effect in the form of an increase in peak tension. TQ administration did not result in cardiac hypertrophy or an increased cardiac metabolic demand at the studied dose. TQ may be a promising inotropic agent.

The association of adiposity, physical fitness, vitamin D levels and haemodynamic parameters in young Saudi females.

OBJECTIVES: In this study, we assessed the possible association of adiposity, physical fitness, vitamin D levels and haemodynamic parameters as intermediate risk factors for cardiovascular health in young Saudi women. METHODS: A total of 87 young healthy Saudi women were recruited in this cross-sectional study during 2014-2015. The body weight, height, waist and hip circumference, and plasma 25-hydroxyvitamin D (25[OH] D) levels were measured. The exercise stress test was performed to determine the pulse rate, blood pressure (BP), ECG, and VO2max. Multiple linear regression models were generated for the resting (r) and maximum (m) diastolic (D) and systolic (s) arterial BP and pulse rate (PR), adiposity markers, VO2max, and plasma levels of 25(OH) D. RESULTS: A multiple linear regression model was significant for the rDBP, mDBP, rSBP, and mSBP with adjusted R2 (6.5, 10.2, 8.3, and 4.5%, respectively). Except for VO2max in the mDBP model, none of the included risk factors were significant according to the t-test. CONCLUSION: This study showed the association of high adiposity and decreased physical fitness with haemodynamic parameters in young Saudi women. An exaggerated exercise DBP might predict future cardiovascular risk in unfit young women.

Effects of two-months Nigella sativa supplementation on cardiac hemodynamics and adrenergic responsiveness.

OBJECTIVE: To study the effects of two, months Nigella sativa (N. sativa) oral supplementation to normal rats on cardiac haemodynamics in vivo, the ionotropic and chronotropic properties of the isolated hearts in vitro, and the cardiac responsiveness to progressive adrenergic stimulation by isoproterenol. METHODS: The cardiac workload, after 2 months of N. sativa oral supplementation to normal adult rats, was assessed in vivo by measuring the cardiac pressure-rate product (mean arterial blood pressure multiplied by heart rate). Cardiac performance in vitro was evaluated by calculating the tension-rate product (developed peak tension multiplied by heart rate). The cardiac inotropic and chronotropic adrenergic responsiveness of N. sativa supplemented rats were evaluated in a Langendorff heart model upon graded infusion of the beta-adrenergic agonist isoproterenol. RESULTS: The isolated hearts of Nigella-treated rats maintained their normal cardiac adrenergic responsiveness, with a selective enhancement of both the tension-rate product and the inotropic reserve. In contrast, the in vivo cardiac pressure-rate product in N. sativa supplemented rats was not significantly different from the control group. CONCLUSION: The demonstrated favourable results of N. sativa supplementation on the intrinsic cardiac contractile properties without evidence of an increased cardiac work load or energy consumption in vivo makes N. sativa an attractive inotropic agent with an economic haemodynamic profile. Further research is recommended to explore the usefulness of N. sativa in cardiovascular disorders associated with systolic dysfunction.