Multiple Myeloma: A Personal Account of My Journey With the Disease and Response to Teclistamab.

Multiple myeloma (MM) remains an incurable hematologic cancer leading to damage to the bone marrow that causes destructive bone lesions in addition to many other effects. I am a patient with MM who has undergone treatment to date since the diagnosis of this disease in December 2019. This paper reviews the treatments and observations made throughout this period. The salient results of such treatments are discussed in chronological order. During this period, my MM relapsed and then I was introduced to teclistamab treatment. The outcome of teclistamab treatment is quite promising, and I anticipate a longer life at a maintenance dose of this drug with a better quality of life. When writing this article, I am still receiving the teclistamab treatment cycles that maintain a constant normal level of my kappa-free light chain (FLC) and kappa/lambda ratio, with no significant side effects.

Defocused and Radial Shock Wave Therapy, Mesotherapy, and Kinesio Taping Effects in Patients with Lipedema: A Pilot Study.

The aim of this pilot study was to investigate the effects of defocused and radial shock wave therapy, mesotherapy, and kinesio taping on pain, circumferences of lower limbs, echographic/ elastosonographic pattern of subcutaneous adipose tissue (SAT), and quality of life in patients with lipedema. Fifteen women affected by lower limb lipedema in stage II were treated with shock wave therapy, mesotherapy, and kinesio taping on thighs and legs (eight sessions, twice a week). The primary outcome was pain, as assessed by Numeric Rating Scale (NRS). Secondary outcomes included the limb circumferences measurements, the SF-12 Health Survey for quality of life, the International Classification of Functioning (ICF) for disability, and echographic/ elastosonographic changes of SAT. Significant reductions of pain and circumference measurements were seen in patients at each follow up. This was associated with significant reduction of thickness, echographic pattern improvement, and increased elasticity of SAT, with consequent positive impact on the quality of life and disability reported by the patients. The results demonstrate improved clinical and functional ultrasound findings in patients affected by lipedema in the early stages of lower limbs, and this combination therapy needs to be investigated in larger populations at multiple centers to confirm the findings.

Survival and Epidemiologic Trends of Lymphomas in Saudi Arabia: A 10-Year Report from a Tertiary Care Hospital.

Background: The current trends in lymphoma cases from Saudi Arabia and their long-term survival are unknown. This study was conducted to evaluate the trends of lymphoma diagnoses and survival from a major tertiary care hospital in Saudi Arabia. Methods: This retrospective study included all new cases of lymphoma diagnosed in adults (age ≥18 years) at King Saud University Medical City, Riyadh, Saudi Arabia, from 2008 to 2018, as identified from the Saudi Cancer Registry. Data on the demographics and clinical characteristics were collected, the survival outcomes were estimated, and multivariate analysis of the overall survival was calculated. Results: A total of 422 patients were included (median age: 46 years). The number new cases of lymphoma diagnosed variably increased over the study period: From 28 (7%) cases in 2009 to 48 (11%) in 2018. The most common lymphoma was diffuse large B-cell lymphoma (175; 41%): and extranodal site was GI involvement (33.5%). In terms of survival, 79% were alive at the last follow-up. On multivariable analysis, the hazard ratio (HR) for patients aged ≥60 years was 3.44 (95% CI: 2-5.9; P = 0.0000069), adjusted for lactate dehydrogenase level (LDH) and disease stage. For advanced-stage disease and high LDH, the HR was 4.2 (95% CI: 1.5-11.8, P = 0.00637) and 0.5 (95% CI: 0.28-0.97; P = 0.04106), respectively. Conclusions: The lymphoma trend in the Saudi Arabian population showed variable increase in cases over the study period, with most patients presenting with advanced-stage disease and at a younger age. The overall survival was comparable with studies from Western countries.

High Prevalence of Bone Marrow Involvement and Advanced Disease in Saudi Patients Diagnosed With Hodgkin Lymphoma.

Objectives To estimate the current prevalence of bone marrow involvement in classical Hodgkin lymphoma (HL) patients diagnosed at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. Methods A cross-sectional study was conducted among classical Hodgkin's lymphoma patients, diagnosed between 2015 and 2021 at KKUH. We retrospectively collected clinical and pathological information from all adult patients aged 18 years or older with a diagnosis of HL. Survival analyses were performed using the log-rank test and Kaplan-Meier curves. Results The study included 140 patients, 60 (42.86%) of whom were female. Bone marrow involvement was seen in 15 (10.71%) patients, 58 (41.43%) patients had an advanced-stage disease, and 20 (14.29%) patients had gastrointestinal involvement. Patients with bone marrow involvement had a median survival of 71 months (95% confidence interval (CI): 16.7-125.3) compared to patients without bone marrow involvement who had a median survival of 68 months (95% CI: 50.7-85.3). Conclusion The prevalence of bone marrow involvement in HL patients, as well as the proportion of patients presenting with advanced disease at the time of diagnosis, was higher compared to Western data. This could be attributed to a delay in diagnosis or more aggressive disease biology.

Quality assessment of evidence-based clinical practice guidelines for the management of pregnant women with sickle cell disease using the AGREE II instrument: a systematic review.

BACKGROUND: The management of pregnant women with sickle cell disease (SCD) poses a major challenge for maternal healthcare services owing to the potential for complications associated with morbidity and mortality. Trustworthy evidence-based clinical practice guidelines (CPGs) have a major impact on the positive outcomes of appropriate healthcare. The objective of this study was to critically appraise the quality of recent CPGs for SCD in pregnant women. METHODS: Clinical questions were identified and the relevant CPG and bibliographic databases were searched and screened for eligible CPGs. Each CPG was appraised by four independent appraisers using the AGREE II Instrument. Inter-rater analysis was conducted. RESULTS: Four eligible CPGs were appraised: American College of Obstetricians and Gynecologists (ACOG), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Health and Care Excellence (NICE), and Royal College of Obstetricians and Gynaecologists (RCOG). Among them, the overall assessments of three CPGs (NICE, RCOG, NHLBI) scored greater than 70%; these findings were consistent with the high scores in the six domains of AGREE II, including:[1] scope and purpose,[2] stakeholder involvement,[3] rigor of development,[4] clarity of presentation,[5] applicability, and [6] editorial independence domains. Domain [3] scored (90%, 73%, 71%), domain [5] (90%, 46%, 47%), and domain [6] (71%, 77%, 52%) for NICE, RCOG, and NHLBI, respectively. Overall, the clinical recommendations were not significantly different between the included CPGs. CONCLUSIONS: Three evidence-based CPGs presented superior methodological quality. NICE demonstrated the highest quality followed by RCOG and NHLBI and all three CPGs were recommended for use in practice.

Effect of the methanol extract of the red cultivar Allium cepa L. on the serum biochemistry and electrolytes of rats following sub-chronic oral administration.

Background In traditional medicine, Allium cepa Linnaeus is used for the treatment of several disease conditions. Whilst reports abound on the effects of several cultivars of A. cepa L on biochemical parameters, similar information on the red cultivar is scarce. This study examines the effects of the methanol extract of the red cultivar A. cepa L on some serum biochemical parameters in experimental Wistar rats. Materials and methods Fifty-five Wistar rats were divided into three groups (A, B and C), which include 25, 25 and 5 rats, respectively. The rats in Groups A and B were sub-divided into 5 groups of 5 rats. Each rat was administered a certain dose of methanol extract of the red cultivar A. cepa L for 14 days (Group A) or 28 days (Group B). Group C rats served as the control and were administered with distilled water (10 mL/kg). Results A. cepa L administration resulted in dyslipidaemia, hyponatremia, hypokalaemia and hyperchloraemia; a significant (p < 0.05) decrease in hepatic enzymes and a significant (p < 0.05) increase in serum bicarbonate, bilirubin and its fractions. Conclusions These biochemical results indicate that the excessive and prolonged medicinal consumption of A. cepa L products beyond 7 days may induce moderate hepatic injury and mild renal dysfunction and may complicate disease conditions, such as hypertension and diabetes. Thus, in order to minimize its toxic effects, it is recommended that A. cepa L products should not be used for more than seven consecutive days or beyond a dosage of 90 mg/kg.

Using advanced wound care and hyperbaric oxygen to manage wound complications following treatment of vulvovaginal carcinoma.

Postoperative management of patients with vulvar cancer is associated with a high incidence of poor wound healing and radiation -induced late tissue necrosis. This case series demonstrates the impact on wound healing with the use of hyperbaric oxygen therapy and advanced wound care following radical vulvectomy and/or radiation therapy. A retrospective case series was performed of all patients from 2016 to 2017 with lower genital cancer who underwent radical surgery with or without chemoradiation treatment, experienced wound dehiscence or late tissue radionecrosis, and were treated with advanced wound care, including hyperbaric oxygen therapy (HBO). Five patients were included with a mean age of 63; four had squamous cell carcinoma and one patient had vaginal adenocarcinoma secondary to prior diethylstilbestrol exposure. Three patients underwent radical vulvectomy. All received pelvic radiation therapy, subsequently experienced wound complications, and were managed with advanced wound care and HBO. The mean reduction in wound area at the final wound follow up visit after completion of HBO therapy was found to be 76%, ranging 42-95%, with an average follow up of five months. The mean number of HBO sessions per patient was 58. Complete tissue granulation or significant improvement in tissue radionecrosis was present in all patients. Advanced wound care and hyperbaric oxygen therapy are beneficial in the management of postoperative wound complications. Prospective studies are needed to identify the optimal use of perioperative hyperbaric oxygen and appropriate wound care for patients with gynecologic malignancies.

Nicergoline inhibits human platelet Ca(2+) signalling through triggering a microtubule-dependent reorganization of the platelet ultrastructure.

BACKGROUND AND PURPOSE: Recently, we demonstrated that a pericellular Ca(2+) recycling system potentiates agonist-evoked Ca(2+) signalling and granule secretion in human platelets and hypothesized a role for the membrane complex (MC) in orchestrating the accumulation of Ca(2+) in the pericellular region. Previous work has demonstrated that treatment with high concentrations of nicergoline may disrupt the MC through an ability to trigger a re-organization of the dense tubular system. Experiments were therefore performed to assess whether nicergoline-induced changes in platelet ultrastructure affects thrombin-evoked Ca(2+) fluxes and dense granule secretion. EXPERIMENTAL APPROACH: Thrombin-evoked Ca(2+) fluxes were monitored in Fura-2- or Fluo-5N-loaded human platelets, or using platelet suspensions containing Fluo-4 or Rhod-5N K(+) salts. Fluorescence microscopy was utilized to monitor microtubule structure and intracellular Ca(2+) store distribution in TubulinTracker- and Fluo-5N-loaded platelets respectively. Dense granule secretion was monitored using luciferin-luciferase. KEY RESULTS: Nicergoline treatment inhibited thrombin-evoked Ca(2+) signalling and induced alterations in the microtubule structure and the distribution of intracellular Ca(2+) stores in platelets. Nicergoline altered the generation and spreading of thrombin-induced pericellular Ca(2+) signals and almost completely prevented dense granule secretion. Stabilization of microtubules using taxol reversed most effects of nicergoline on platelet Ca(2+) signalling and partially reversed its effects on dense granule secretion. CONCLUSIONS AND IMPLICATIONS: Nicergoline-induced alterations to platelet ultrastructure disrupt platelet Ca(2+) signalling in a manner that would be predicted if the MC had been disrupted. These data suggest that nicergoline may be a useful prototype for the discovery of novel MC-disrupting anti-thrombotics.

Contact lens-related microbial keratitis in deployed British military personnel.

AIMS: To quantify the effect of contact lens-related microbial keratitis (CLMK) in the British Defence personnel particularly those in active service in the Arabian Gulf and Afghanistan between June 2001 and January 2007. METHODS: A retrospective review of all British military personnel who developed contact lens-related keratitis during deployment. RESULTS: A total of 27 cases (27, eyes, 23, male; median age 26 (range 19-41) years) were identified, of whom 19 cases were evacuated from Iraq alone. Twenty cases were associated with soft contact lens wear. Seven cases were culture positive, of which five grew Pseudomonas aeruginosa. The overall incidence of CLMK in contact lens wearer in the British military in Iraq was 35 per 10,000. There was an increased incidence during the summer months. Seventeen eyes (63%) lost more than one line of visual acuity with a resultant permanent medical downgrading in duty capability in nine cases. CONCLUSIONS: CLMK has a poorer outcome in a deployed military environment when compared to the civilian setting. Increased awareness of the health risks of contact lens wear together with standardised treatment regimens based on improved pathogen detection using molecular diagnostics have improved outcomes.

Ocular manifestations in oculodentodigital dysplasia resulting from a heterozygous missense mutation (L113P) in GJA1 (connexin 43).

PURPOSE: To characterize the ophthalmic findings, intrafamilial variability, and molecular genetic basis of oculodentodigital dysplasia (ODDD; MIM no. 164200). METHODS: Ophthalmic examination included best-corrected visual acuity, slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, Goldmann applanation tonometry and A-scan ultrasonography. Blood samples were taken for DNA extraction and mutation screening of GJA1 (connexin 43). RESULTS: All three affected individuals had characteristic features of ODDD. The ophthalmic features were epicanthus, microcornea, and the presence of glaucoma. The ocular phenotype resulted from a heterozygous T>C transition at nucleotide 338 in GJA1 (L113P) that was not detected in 120 chromosomes of unaffected individuals. The L113P mutation results in a nonconservative substitution in the cytoplasmic loop of Cx43 (GJA1) and is predicted to disrupt the high-order structure of Cx43. CONCLUSIONS: This report describes the ocular phenotype in a molecularly characterized ODDD syndrome family. The ocular features in this family highlight the key role Cx43 plays in eye development and in the development of glaucoma. L113P represents a pathogenic mutation in GJA1 (Cx43) and results in ODDD with marked intrafamilial variation in glaucoma type and severity.

Histologic evaluation of the glenohumeral joint capsule after radiofrequency capsular shrinkage for atraumatic instability.

We evaluated histologically 10 biopsy specimens taken preoperatively from the anterior-inferior glenohumeral ligament from patients with atraumatic instability who had undergone radiofrequency capsular shrinkage, 10 taken immediately postoperatively, and 13 taken before revision. The synovial and subsynovial layers returned to normal histology in biopsy specimens taken from 6 months onwards. Collagen bundles in the fibrous layer continued to have a reparative histology during the period of the study (up to 37 months). The type of radiofrequency probe used (monopolar or bipolar) had no effect on the histologic healing process (P > 0.5, chi2 test). A histologic score was introduced, and this was found to have an excellent intraobserver agreement (weighted kappa, 0.840) and a moderate interobserver agreement (weighted kappa, 0.698).

Choroidal effusion and hypotony caused by severe anterior lens capsule contraction following cataract surgery.

PURPOSE: The case report describes a case of severe anterior capsular contraction associated with choroidal effusion. CASE REPORT: An 81 year old female with primary open angle glaucoma underwent routine phacoemulsification cataract surgery. Eight weeks following surgery the anterior capsule opening had reduced to 3 mm in size. Intraocular pressure was found to be 4 mmHg and B scan ultrasound revealed a large choroidal effusion. Anterior capsulotomy with Nd:YAG laser was performed. At review, two weeks later, the choroidal effusion had resolved and visual acuity had recovered. DISCUSSION: The Nd:YAG laser radial relaxing capsulotomies helped relieve the capsular contraction and associated traction on the ciliary body.

Effects of luteinizing hormone, follicle-stimulating hormone, and epidermal growth factor on expression and kinase activity of cyclin-dependent kinase 5 in Leydig TM3 and Sertoli TM4 cell lines.

We examined the effects of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and epidermal growth factor (EGF) on the expression and kinase activity of cyclin-dependent kinase 5 (Cdk5) in Leydig TM3 and Sertoli TM4 cell lines. Hormonal regulation of the expression and activity of Cdk5 by using normal and hypophysectomized rat testes was also investigated to elucidate its role. Cdk5 levels and kinase activity were significantly elevated in TM3 cells that were grown in the presence of 7.5% serum, EGF, or LH and were associated with an increase in testosterone production compared with controls. These increases were accompanied by an increase in proliferation of TM3 cells after treatment with serum or EGF but not with LH suggest that Cdk5 may be involved in cellular differentiation that is induced with LH treatment. In contrast, the presence of neither serum, EGF, nor FSH had a significant effect on Cdk5 activity levels in the Sertoli TM4 cell line, and there was no correlation with proliferative activity or transferrin levels. A significant decrease in Cdk5 expression and activity were noted in rat testis after hypophysectomy compared with normal rat testis and is associated with a simultaneous decrease in testosterone and transferrin levels. Immunohistochemical analysis revealed that Cdk5 was strongly expressed in the nuclei and cytoplasm of Leydig cells, Sertoli cells, spermatogonia, and peritubular cells of normal adult rat testis. After hypophysectomy, the pattern of Cdk5 staining differed markedly from that in normal rat testis and a profound reduction in staining of Cdk5 was observed in each tubule. Our results suggest that LH and EGF influence and modulate Cdk5 expression and activity in Leydig TM3 cells and may, conceivably, be involved in signal transduction cascades that are initiated by hormones or growth factors. Cdk5 in Sertoli TM4 cells is likely to possess some constitutive functions that are not affected by the cells' proliferation state. Moreover, Cdk5 is probably involved in the constitutive and hormonally stimulated activities of the rat testis, in addition to its involvement in cell proliferation.

Expression of cyclin-dependent kinase 5 and associated cyclins in Leydig and Sertoli cells of the testis.

In this study, we examined the expression and subcellular localization of cyclin-dependent kinase 5 (Cdk5), cyclin D1, and cyclin E in Leydig and Sertoli cell lines that were cultured with 7.5, 1.0, 0.5, or 0% serum (mixture of a 2:1 ratio of horse serum and fetal bovine serum) and in the developing rat testis to verify the possible functions of Cdk5, cyclin D1, and cyclin E in the testis. The abundance of Cdk5 and cyclin E in the Leydig cell line, TM3, was significantly reduced at low serum concentrations. In contrast, serum concentration had no effect on Cdk5 and cyclin E levels in the Sertoli cell line, TM4. Cyclin D1 was detected by western blot analysis in TM4 cells only, and its abundance was serum dose dependent. The kinase activity of Cdk5 in TM3 and TM4 cells that were cultured at various serum concentrations coincided with the levels of Cdk5 expression. Immunohistochemical staining for Cdk5 and cyclin E revealed nuclear and cytoplasmic distribution, both in TM3 and TM4 cells. Moreover, cyclin D1 immunoreactivity was only detected in TM4 cells. In the developing rat testis, Cdk5 expression was most prominent at 2 and 3 weeks after birth. Cyclin D1 was strongly expressed at 1 and 2 weeks in premature rat testes. On the other hand, cyclin E was highly expressed in the adult testis. Immunohistochemical localization of Cdk5, cyclin D1, and cyclin E in 1-week-old and adult rat testes revealed expression in both Leydig and Sertoli cells. Our results suggest that Cdk5 in TM3 and Leydig cells of the testis might play a role in cell cycle regulation, whereas Cdk5 in TM4 and Sertoli cells of the adult testis might have some additional functions besides control of proliferation.

Endoscopic suspension of bladder neck for treatment of female stress urinary incontinence.

Between the years 1984 and 1993, a total of 72 female patients underwent endoscopic suspension of bladder neck for treatment of stress urinary incontinence at the King Hussein Medical Center and Hamad General Hospital, Amman, Jordan. The age of the study patients ranged between 32 and 75 years (mean: 46.5 years). Fifteen (20.8%) had history of previous operations for incontinence. The overall success rate achieved was 93.1%. Post-operative complications were encountered in seven (9.8%) patients within follow-up period of 4 to 43 months. Treatment failure occurred in five patients (6.9%). Our experience further confirms that endoscopic suspension of the bladder neck is a simple and reliable procedure in the treatment of female stress urinary incontinence.