Hereditary vitamin D resistant rickets (HVDRR) case series: phenotype, genotype, conventional treatment, and adjunctive cinacalcet therapy.

INTRODUCTION: Hereditary vitamin D resistant rickets (HVDRR) is a rare autosomal recessive disorder marked by end-organ resistance of 1,25-dihydroxyvitamin D secondary to various mutations in the vitamin D receptor gene. The currently accepted treatment modality involves bypassing the affected receptors in the gut with high-dose intravenous calcium. In a few limited case reports, cinacalcet, a calcimimetic, has been used as an adjunctive therapy. MATERIAL AND METHODS: Retrospective chart reviews were conducted to collect the clinical and biochemical data of 8 patients with HVDRR from 5 Saudi families. Four patients received only high-dose calcium, while the remaining 4 received adjuvant cinacalcet. Serum chemistry and PTH levels were measured before and during cinacalcet treatment. Gene sequencing was performed to identify the disease-causing mutation. RESULTS: All 8 patients exhibited alopecia and secondary hyperparathyroidism. Other clinical and biochemical features of rickets were present to varying degrees. Genetic analysis revealed 3 distinct mutations: a ligand-binding domain mutation in 3 unrelated patients, a ligand-binding domain mutation in 2 sisters, and a missense DNA-binding domain mutation in 3 brothers. While the overall response to therapy was variable, none of the 4 patients who received adjunctive cinacalcet developed hypocalcaemia, and there was some initial promise in improving serum PTH levels. CONCLUSIONS: This series provides new insight into the clinical and biochemical characteristics as well as treatment responses in Saudi children with HVDRR. The findings suggest that cinacalcet is a safe and potentially valuable adjuvant in this understudied population; however, further research is required to verify these results.

The Characteristics and Outcomes of Nonhospitalized Patients With Heart Failure in Saudi Arabia: A Contemporary Single-Center Study.

Background Contemporary data on patients with heart failure (HF) in Saudi Arabia is limited. Methods This was a retrospective study of patients who were followed in the HF Clinic at our center after January 1, 2022. The study end date was August 31, 2023. Patients who were alive and followed for <6 months were excluded. We reported the clinical characteristics, utilization of established therapies for HF, proportion of potential candidates for ancillary HF treatments, and rates of HF events and mortality. Results A total of 202 patients met the study criteria. The mean age was 56.0 ± 15.2 years. The median follow-up from the initial visit to the study end date was 47 months (interquartile range {IQR}: 29-58 months). Coronary artery disease (CAD) was the cause of HF in 85 (42%) patients. At their latest visit, 103 (51%) patients had diabetes, 82 (41%) were obese, and 134 (66%) received quadruple therapy. Iron deficiency was present in 143 (71%) patients during follow-up. At their latest visit, moderate-to-severe or severe functional mitral regurgitation (MR) and hyperkalemia were present in 15 (7%) and 20 (10%) patients, respectively. The combined annual rate of HF hospitalization and emergency visits for HF was 20%. At least one hospitalization for HF within a year before the study end date occurred in 19 (9%) patients. The annual all-cause mortality was 1.8%. Conclusion This contemporary cohort of outpatients with HF was relatively young and had a high prevalence of diabetes, obesity, and iron deficiency. An estimate of potential candidates for iron replacement, transcatheter repair of the mitral valve, novel potassium binders, and the implantation of the pulmonary artery pressure monitor was among the first reported regionally. All-cause mortality was low, yet the burden of HF-related events was significant.

Percent fluid overload for prediction of fluid de-escalation in critically ill patients in Saudi Arabia: a prospective observational study.

BACKGROUND: Percent fluid overload greater than 5% is associated with increased mortality. The appropriate time for fluid deresuscitation depends on the patient's radiological and clinical findings. This study aimed to assess the applicability of percent fluid overload calculations for evaluating the need for fluid deresuscitation in critically ill patients. METHODS: This was a single-center, prospective, observational study of critically ill adult patients requiring intravenous fluid administration. The study's primary outcome was median percent fluid accumulation on the day of fluid deresuscitation or intensive care unit (ICU) discharge, whichever came first. RESULTS: A total of 388 patients was screened between August 1, 2021, and April 30, 2022. Of these, 100 with a mean age of 59.8±16.2 years were included for analysis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15.4±8.0. Sixty-one patients (61.0%) required fluid deresuscitation during their ICU stay, while 39 (39.0%) did not. Median percent fluid accumulation on the day of deresuscitation or ICU discharge was 4.5% (interquartile range [IQR], 1.7%-9.1%) and 5.2% (IQR, 2.9%-7.7%) in patients requiring deresuscitation and those who did not, respectively. Hospital mortality occurred in 25 (40.9%) of patients with deresuscitation and six (15.3%) patients who did not require it (P=0.007). CONCLUSIONS: The percent fluid accumulation on the day of fluid deresuscitation or ICU discharge was not statistically different between patients who required fluid deresuscitation and those who did not. A larger sample size is needed to confirm these findings.

Molecular epidemiology and outcome of carbapenem-resistant Enterobacterales in Saudi Arabia.

BACKGROUND: The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers. METHODS: This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables. RESULTS: A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26-6.24), p = 0.01]. CONCLUSIONS: These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.

Outpatient fractionated ICE protocol in relapsed/refractory lymphomas: Efficacy and safety.

METHODS: In this retrospective trial, we analyzed data of patients with relapsed/refractory lymphoma who received outpatient fractionated ICE between 2011-2017 at a tertiary care center. The three weekly ICE protocol consisted of: ifosfamide 1500 mg/m2 infused over 2 h on days 1-3, carboplatin (5 AUC) on day 1, and etoposide 100 mg/m2 on days 1-3. Rituximab 375 mg/m2 was given to patients with CD20 positive B cell Non-Hodgkin lymphoma. RESULTS: Total of 89 patients were included in this research project. Majority of patients had Hodgkin lymphoma (64%). Mean number of ICE cycles received was 2.5. Complete remission and partial remission rates for primary refractory (62.9%) and non-primary refractory (36.4%) disease were 10.5% and 26.3% versus 41.9% and 29.0% respectively. Event free survival rate was 14.5 months (95% CI 7.7-28.0) and overall survival rate 88.7 months (95% CI 48.1-NR). Grade 3 hematological toxicities were documented in 19.1% of patients with 10.1% experiencing neutropenia and 9% thrombocytopenia. 5.6% had febrile neutropenia. CONCLUSIONS: Our study included, to our knowledge, the largest number of patients treated with outpatient fractionated ICE. Results demonstrated that this regimen might be a reasonable replacement for classic ICE regimen in many patients with lymphoma. It has a favorable safety profile. However, patients with primary refractory lymphomas need more effective regimens.

Hospitalizations following living donor nephrectomy in the United States.

BACKGROUND AND OBJECTIVES: Living donors represented 43% of United States kidney donors in 2012. Although research suggests minimal long-term consequences of donation, few comprehensive longitudinal studies for this population have been performed. The primary aims of this study were to examine the incidence, risk factors, and causes of rehospitalization following donation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: State Inpatient Databases (SID) compiled by the Agency for Healthcare Research and Quality were used to identify living donors in four different states between 2005 and 2010 (n=4524). Multivariable survival models were used to examine risks for rehospitalization, and patient characteristics were compared with data from the Scientific Registry of Transplant Recipients (SRTR). Outcomes among patients undergoing appendectomy (n=200,274), cholecystectomy (n=255,231), and nephrectomy for nonmetastatic carcinoma (n=1314) were contrasted. RESULTS: The study population was similar to United States donors (for SRTR and SID, respectively: mean age, 41 and 41 years; African Americans, 12% and 10%; women, 60% and 61%). The 3-year incidence of rehospitalization following donation was 11% for all causes and 9% excluding pregnancy-related hospitalizations. After censoring of models for pregnancy-related rehospitalizations, older age (adjusted hazard ratio [AHR], 1.02 per year; 95% confidence interval [95% CI], 1.01 to 1.03), African American race (AHR, 2.16; 95% CI, 1.54 to 3.03), depression (AHR, 1.88; 95% CI, 1.12 to 3.14), hypothyroidism (AHR, 1.63; 95% CI, 1.06 to 2.49), and longer initial length of stay were related to higher rehospitalization rates among donors. Compared with living donors, adjusted risks for rehospitalizations were greater among patients undergoing appendectomy (AHR, 1.58; 95% CI, 1.42 to 1.75), cholecystectomy (AHR, 2.25; 95% CI, 2.03 to 2.50), and nephrectomy for nonmetastatic carcinoma (AHR, 2.95; 95% CI, 2.58 to 3.37). Risks for rehospitalizations were higher among African Americans than whites in each of the surgical groups. CONCLUSIONS: The SID is a valuable source for evaluating characteristics and outcomes of living kidney donors that are not available in traditional transplant databases. Rehospitalizations following donor nephrectomy are less than seen with other comparable surgical procedures but are relatively higher among donors who are older, are African American, and have select comorbid conditions. The increased risks for rehospitalizations among African Americans are not unique to living donation.

Comorbidity burden and perioperative complications for living kidney donors in the United States.

BACKGROUND AND OBJECTIVES: Since 1998, 35% of kidney transplants in the United States have been derived from living donors. Research suggests minimal long-term health consequences after donation, but comprehensive studies are limited. The primary objective was to evaluate trends in comorbidity burden and complications among living donors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The National Inpatient Sample (NIS) was used to identify donors from 1998 to 2010 (n=69,117). Comorbid conditions, complications, and length of stay during hospitalization were evaluated. Outcomes among cohorts undergoing appendectomies, cholecystectomies and nephrectomy for nonmetastatic carcinoma were compared, and sample characteristics were validated with the Scientific Registry of Transplant Recipients (SRTR). Survey regression models were used to identify risk factors for outcomes. RESULTS: The NIS captured 89% (69,117 of 77,702) of living donors in the United States. Donor characteristics were relatively concordant with those noted in SRTR (mean age, 40.1 versus 40.3 years [P=0.18]; female donors, 59.0% versus 59.1% [P=0.13]; white donors, 68.4% versus 69.8% [P<0.001] for NIS versus SRTR). Incidence of perioperative complications was 7.9% and decreased from 1998 to 2010 (from 10.1% to 7.6%). Men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 1.20 to 1.56) and donors with hypertension (AOR, 3.35; 95% CI, 2.24 to 5.01) were more likely to have perioperative complications. Median length of stay declined over time (from 3.7 days to 2.5 days), with longer length of stay associated with obesity, depression, hypertension, and pulmonary disorders. Presence of depression (AOR, 1.08; 95% CI, 1.04 to 1.12), hypothyroidism (AOR, 1.07; 95% CI, 1.04 to 1.11), hypertension (AOR, 1.38; 95% CI, 1.27 to 1.49), and obesity (AOR, 1.07; 95% CI, 1.03 to 1.11) increased over time. Complication rates and length of stay were similar for patients undergoing appendectomies and cholecystectomies but were less than those with nephrectomies for carcinoma. CONCLUSIONS: The NIS is a representative sample of living donors. Complications and length of stay after donation have declined over time, while presence of documented comorbid conditions has increased. Patients undergoing appendectomy and cholecystectomy have similar outcomes during hospitalization. Monitoring the health of living donors remains critically important.

Intimate partner violence victimization and perpetration by Puerto Rican women with severe mental illnesses.

Previous research indicates a higher prevalence of victimization among severely mentally ill women. Few studies have either compared these levels across diagnostic categories or evaluated perpetration by the women. We report qualitative and quantitative findings regarding intimate partner violence perpetrated both against and by a sample of 53 Puerto Rican women diagnosed with major depression, bipolar disorder, or schizophrenia. Interviewers shadowed participants for a period of 2 years. Two-thirds of the women with serious mental illness had histories of victimization. However, 23% of the women also reported histories of violence towards their significant others. This was attributed to various reasons, such as anger, revenge, control, and self-defense. Participants described their personal conceptualization of the violence they received and perpetrated. This has implications for programs designed to prevent family violence, for health care professionals in general, and for psychiatrists, who may be called upon to address future risk of victimization or commission of violence.

Comparing two approaches to acquiring HIV-risk data from Puerto Rican women with severe mental illness.

Renewed interest has been expressed by researchers in mixed-method assessment that employs both quantitative and qualitative techniques in an expansive style that utilizes a variety of tactics to address research questions. Participants consisted of Puerto Rican women with severe mental illness living in Cuyahoga County, Ohio. The women were shadowed over a 2-year period to observe and verify behaviors that were self-reported using standardized instruments in semi-structured interviews. Concurrent criterion-related validity was employed to determine the extent of the correlation between responses obtained from the two approaches. Forty-four percent of the women were diagnosed with major depression and the mean overall GAF score was 58.5 +/- 14.5. A comparison of the data collected using the different methodologies revealed that inconsistent and contradictory responses are not uncommon. The mixed-method design provided a more complete way of obtaining HIV-risk behavior data. Researchers and clinicians could benefit from mixed methods research that can provide greater opportunities to obtain data of a sensitive nature.