Challenges and Uncertainties in the Diagnosis of Cardiac Amyloidosis: A Case Report.

Amyloidosis is the condition when starch-like misfolded proteins form insoluble fibrils that deposit in tissues and cause dysfunction. Cardiac amyloidosis occurs due to the deposition of amyloid fibrils at the cardiac level and is an important cause of heart failure. This case reveals a patient with significant heart failure and arrhythmia, which later on turned out to be caused by cardiac amyloidosis. While regarded as a rare disease in practice, in retrospect, there are a lot of signs and imaging indicators, particularly in echocardiography that warrant an investigation of cardiac amyloidosis. In this case review, red flags in echocardiography that should endorse further testing for underlying cardiac amyloidosis are highlighted.

Total hip arthroplasty for adult patients with hip arthritis in Jordan: clinical profiles and patient characteristics.

PURPOSE: Total Hip Arthroplasty (THA) is one of the most commonly performed orthopaedic surgeries, with hip arthritis being the main indication. This procedure is usually performed when other non-surgical methods fail to relieve patients' hip pain and improve their quality of life. However, limited information exists to identify and compare the demographics and clinical characteristics of patients undergoing this procedure in Jordan. This study aims to identify these demographic and clinical characteristics and compare the findings in terms of gender differences. METHODOLOGY: This is a retrospective study that analysed the hospital records of 650 patients undergoing THA in tertiary referral hospital in Jordan over a four-year period from January 2019 to December 2022. The collected data were classified into three categories: demographic characteristics, perioperative variables, and patients' related health profiles. IBM's Statistical Package for the Social Sciences (SPSS) version 23 software (IBM, USA) and descriptive analysis were used for data analysis. RESULTS: Two-thirds of the sample studied were female (63.4%). In terms of bleeding profiles, the mean intraoperative blood loss was 542 millilitres. The major indication for THA was degenerative hip arthritis (50.5%), followed by hip dysplasia (40.3%).. Comparing the findings of the two gender groups, females were more likely to have degenerative and dysplastic hip arthritis (221 and 157, p = 0.04 and p = 0.1, respectively) when compared to males. Although males were more likely to lose more blood during the surgery (557 ml vs. 533 ml, p = 0.33, females needed more blood transfusions both during (21 vs. 6 patients, p = 0.12) and after the surgery (57 vs. 16 patients, p = 0.006). Furthermore, females were more likely to have comorbidities such hypertension (293 vs. 179 patients, p = 0.20), and hypothyroidism (313 vs 187, p = 0.36), and diabetes (85 vs. 38 patients, p = 0.15), among many other health conditions. However, in the study sample, male smokers outnumbered female smokers (132 vs. 63). CONCLUSION: Gender highly impacted the immediate surgical outcomes of patients who underwent THA. Females were more likely to need blood transfusions both during and after the surgery and had lower post-operative haemoglobin readings. In addition, females had more comorbidities and degenerative hip osteoarthritis. We believe that raising awareness about comorbidity management, preoperative smoking cessation, and perioperative blood transfusion management can improve medical and surgical outcomes.

The effects of intracellular iron availability on the outcome of Toxoplasma gondii infection in mice.

Toxoplasma gondii (T. gondii) is a parasite that obtains the iron it needs for its own metabolism from the host-cell iron pool. In this work, we aimed to investigate if iron supplementation or deficiency affected the course of T. gondii infection. Eighty mice were divided into four groups, each with 20 animals: Group (I): Uninfected control group. Group (II): Infected control group: injected with Phosphate buffered saline. Group (III): Infected group: received iron sucrose treatment. Group (IV): Infected group: treated with deferoxamine. Quantitative PCR studies were performed on days 3 and 8 post-infection to detect the expression of iron metabolism genes (hamp and ferroprotin) and immune-histochemical analysis to study the percentage of TNF-α and TGF-ß tissue expression. Iron supplementation induced progressions of infection evident by increased tissue expression of pro-inflammatory cytokine TNF-α and downregulation of TGF-ß which is mostly linked to suppression of the inflammatory process caused by T. gondii. Increased expression of TGF-ß and decreased expression of TNF-α was noticed when iron deprivation occurred. On day 3, we noticed increased expression in the hamp gene with iron supplementation while it decreases when the iron supply is low. On the contrary, iron deficiency increased ferroprotin gene expression whereas supplementing decreased it. On day 8, the level of expression of these genes returned to normal levels. These observations document the potential role of iron in controlling toxoplasmosis infection and indicate that the transcription of hamp and ferroprotin in T. gondii-infected cells appears to be regulated by a sophisticated indirect mechanism.

Utility of clinical exome sequencing in a complex Emirati pediatric cohort.

Clinical exome sequencing (CES) has become a routine diagnostic tool in several pediatric subspecialties, with a reported average diagnostic yield of ~25% in this patient poulation. The utility of CES in the United Arab Emirates (UAE) has not been previously investigated, most likely due to the lack of the appropriate tertiary pediatric centers and diagnostic genomic facilities in this country. Here, we report, for the first time, CES findings on a multispecialty pediatric cohort in the UAE (N = 51). This cohort, which was mostly Emirati (86%; 44/51), was followed at Al Jalila Children's Hospital (AJCH), the first and only dedicated tertiary pediatric center in the country. CES demonstrates a high diagnostic yield (41%; 21/51) in this cohort, where 55% (28/51) had previous non-diagnostic genetic testing while for the remaining individuals (45%), CES was the first-tier test. Given the reported high consanguinity rate in this population, 48% of the positive cases (10/21) were due to genes associated with recessive conditions. However, 11 out of 21 positive cases (52%) were due to heterozygous pathogenic variants in genes known to cause dominantly inherited disorders, including a case with a dual diagnosis attributed to two different genes (2%; 1/51), and another case with a novel de novo variant and new phenotypic features for a known gene (2%; 1/51). Overall, we have identified 13 novel clinically significant variants and showed that application of CES as a first-tier test plays a significant role in genetic diagnosis and management of Emirati pediatric patients.

Long-term outcome of the difficult nephrotic syndrome in children.

To determine the long-term outcome of nephrotic syndrome (NS) in children, we studied 48 patients with the NS aged seven months to 12 years at onset and followed for a long period (3-9 years). Consanguinity was positive in 31.2%. Patients' history of atopy was present in 25%, while family history of allergy was present in 18 (37.5%) patients. Renal impairment at initial presentation was observed in 12.5% of the patients. Among 32 biopsied patients, 11 (34.3%) had focal segmental glomerulosclerosis and eight (25%) revealed mesangial IgM nephropathy. Outcome at two years of presentation showed 41.6% patients as frequent relapsers, 39.5% as steroid dependent and 18.7% as steroid resistant. Forty-three patients were available for follow-up after ten years of presentation, 22 (51%) patients had complete remission, 15 (34.8%) were steroid dependent, two (4.6%) developed chronic renal failure and two (4.6%) died. Two patients (4.6%) developed insulin-dependent diabetes mellitus, two (4.6%) had cataract and one (2.3%) had documented peritonitis. In conclusion, the high incidence of steroid-dependent, frequent relapses and steroid resistance in children can be explained by different factors, including consanguinity, atopy and severe presentation at onset of disease. We suggest longer initial treatment at onset for this group of patients. The low incidence of infection in this group needs to be addressed in future studies.

Post renal transplantation tubulopathies in children: a 9-year experience at a tertiary care centre.

To evaluate the incidence of tubulopathies in the long-term follow-up of children post renal transplantation, we reviewed the records of 43 patients from 1987-1996. There were 24 (56%) boys. The age of patients at the time of transplant ranged from 2.7 to 15 years. Eighteen children (78%) had transplantation from cadaver donors (CAD). Thirty-two (74%) patients were transplanted in Saudi Arabia and 11(26%) were transplanted abroad. Significant tubular dysfunction developed in 72% of patients. Renal Tubular Acidosis (RTA) occurred in 23/43 (53%) patients. The patients who received CAD grafts required higher mean dose of bicarbonate and longer duration of therapy compared to living related donors (LRD) recipients ( mean dose of 1.7 Vs 0.5 meq/kg/day and mean duration of 18 Vs 3 (1/2) months, respectively). Hypophosphatemia of various degrees of severity (0.4-0.8 mmol/1) was detected in 12 (28%) patients. Those who received CAD grafts required higher mean dose of phosphate and longer period of therapy than those who received LRD grafts. Hypomagnesemia requiring supplemental magnesium therapy occurred in 4 (9%) patients, all received tacrolimus therapy. In four patients with hypomagnesemia, this was mild and transient. Hypokalemia was found in 5 (11.5%) patients; all had CAD grafts. We conclude that tubulopathies were a frequent complication post renal transplantation in our population. They were more severe in the patients who received CAD grafts. However, the defects were controllable and transient.

Paralysis Episodes in Carbonic Anhydrase II Deficiency.

Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder manifest by osteopetrosis, renal tubular acidosis, and cerebral calcification. Other features include growth failure and mental retardation. Complications of the osteopetrosis include frequent bone fractures, cranial nerve compression, and dental mal-occlusion. A hyper-chloremic metabolic acidosis, sometimes with hypokalemia, occurs due to renal tubular acidosis that may be proximal, distal, or more commonly, the combined type. Such patients may present with global hypotonia, muscle weakness or paralysis. We report a case of CA II deficiency with recurrent attacks of acute paralysis which was misdiagnosed initially as Guillian-Barre syndrome.

Levamisole Therapy as a Second-line Immunosuppressive Agent in Corticosteroid-sensitive Nephrotic Syndrome in Children.

To evaluate the effect of levamisole therapy combined with corticosteroid in children with nephrotic syndrome and frequent relapses (FR) or steroid dependence (SD), we studied retrospectively 24 children (18 boys and six girls) with a mean age of 32 months. Eleven (46%) patients had FR and 13 (54%) had SD. Levamisole was used for a mean period of 8.5 months. The relapse rate decreased from a mean of 4 relapses/year during steroid therapy alone to 1.3 relapses/ year during the combined therapy in 17 (71%) of the patients. Remission was sustained, after discontinuing levamisole, for more than six months in 11 of the 17 responders (65%), and six patients relapsed after discontinuing levamisole. Seven of the 24 study patients (29%) had no response to levamisole. The seven patients who failed to respond to levamisole and the six initial responders who could not maintain remission after discontinuing the drug were treated with cyclophosphamide for 12 weeks. Eight of these patients (61.5%) had remission sustained for a mean duration of 10 months. The FR patients sustained remission for a longer period of time than SD patients in both groups. Levamisole was more effective than cyclophosphamide in patients with the age of onset of the disease above 2 years (10 patients out of 11 (91%). The side effects of levamisole and cyclophosphamide in our patients were transient and manageable. We conclude that levamisole is a safe and effective drug if combined with corticosteroid therapy in children with nephrotic syndrome. Further studies may be required.

Urinary tract infection and vesicoureteral reflux in saudi children.

This is a retrospective study of 82 children with urinary tract infection (UTI) evaluated for the prevalence of vesicoureteral reflux at a community hospital in Riyadh, Saudi Arabia from 1997 to 2000. There were 73 (89%) girls and nine (11%) boys; 58 (71%) were at an age between 1-5 years, 15 (18%) were between 0-1year and nine (11%) were more than 5 years of age. All patients were documented to have UTI by history and laboratory investigations. There were 29 patients (35%) who had acute pyelonephritis at the initial clinical presentation and 53 (65%) had recurrent UTI. Escherichia coli was the isolated bacterium from urine in 79(96.4%) patients. Thirty-four (41.5%) patients had vesicoureteral reflux (VUR); 17 (50%) had it bilaterally and 14 (41%) had renal scarring. There were 9/82 (11%) patients who had renal scarring without reflux. Twenty-six (77%) of the VUR patients had mild to moderate reflux (grade 1-3) and eight (23%) had severe reflux (grade 4-5). Two patients with bilateral reflux had mild to moderate reflux on one side and severe reflux on the other. The age of the patients with VUR was below one year in 11 (32%), between 1 year and 5 years in 21(62%), and between 6 and 12 years in two (6%) patients. There were 11/ 29 (38%) patients with acute pyelonephritis who had reflux. Follow-up of the VUR patients showed that reflux disappeared without surgical intervention in 15 (44%), improved in two (6%) to lower grade and worsened in two (6%) to higher grade. Seven (20.5%) patients underwent ureteral reimplantation; all of them had recurrent UTI and were more than one year of age. While on chemoprophylaxis, two (28%) of the reimplanted patients developed breakthrough infections and the remaining five (72%) had a radiological picture of chronic pyelonephritis. None of the study patients developed new scars, hypertension or renal failure during follow-up; the duration of follow-up was from 5 months to 3 1/2 years and only seven (20.5%) patients had less than one-year follow-up. We conclude that Saudi children with UTI below 7 years of age have high incidence of reflux and scarring especially in patients presenting with acute pyelonephritis. A multi center study is needed to evaluate the size of the problem and its complications in the Saudi children besides screening of the siblings of patients with reflux.