Pulmonary manifestations in a cohort of patients with inborn errors of immunity: an 8-year follow-up study.

BACKGROUND: Inborn errors of immunity (IEIs) are a group of congenital diseases caused by genetic defects in the development and function of the immune system. The involvement of the respiratory tract is one of the most common presentations in IEIs. METHODS: Overall, 117 patients with diagnosed IEIs were followed-up within 8 years at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD). Demographic, clinical, and laboratory data were collected in a questionnaire. Pulmonary function test (PFT), chest X-ray (CXR), and high-resolution computed tomography (HRCT) scans were obtained where applicable. RESULTS: Our study population consisted of 48 (41%) patients with predominantly antibody deficiencies (PADs), 39 (32%) patients with congenital defects of phagocytes, 14 (11.9%) patients with combined immunodeficiency (CID), and 16 (14%) patients with Mendelian susceptibility to mycobacterial diseases (MSMD). . Recurrent pneumonia was the most common manifestation, while productive cough appeared to be the most common symptom in almost all diseases. PFT showed an obstructive pattern in patients with PAD, a restrictive pattern in patients with CID, and a mixed pattern in patients with CGD. HRCT findings were consistent with bronchiectasis in most PAD patients, whereas consolidation and mediastinal lesions were more common in the other groups. CONCLUSIONS: Pulmonary manifestations vary among different groups of IEIs. The screening for lung complications should be performed regularly to reveal respiratory pathologies in early stages and follow-up on already existing abnormalities.

Overtime trend of thyroid hormones and thyroid autoimmunity and ovarian reserve: a longitudinal population study with a 12-year follow up.

BACKGROUND: Ovarian reserve, vital for reproductive function, can be adversely affected by thyroid diseases. Despite alternations of thyroid hormones with ageing, data on interactions between the overtime trend of thyroid functions and ovarian reserve status has rarely been reported. We aimed to examine the overtime trend of thyroid hormones, thyroid peroxidase antibody (TPO Ab) and their associations with ovarian reserve status, identified by levels of age specific anti-mullerian hormone (AMH) in reproductive aged women, who participated in 12-year cohort of Tehran Thyroid Study (TTS). METHODS: Reproductive age women(n = 775) without any thyroid disease or ovarian dysfunction were selected from the Tehran Thyroid Study cohort. Participants were divided into four age specific AMH quartiles (Q1-Q4), Q1, the lowest and Q4, the highest. AMH was measured at the initiation of study and thyroid stimulating hormone (TSH), free T4 (FT4), and TPO Ab were measured at baseline and at three follow up visits. RESULTS: At baseline, there was no statistically significant difference in thyroid hormones between women of the four quartiles, although TPO Ab levels were higher in women of Q1. During the follow ups, FT4 was decreased in all quartiles (p < 0.05), whereas TPO Ab increased in Q1 (p = 0.02). Odds ratio of overall TPO Ab positivity in women of Q1 was 2.08 fold higher than those in Q4. (OR: 2.08, 95%CI: 1.16, 3.72; p = 0.01). CONCLUSION: Women with the lowest ovarian reserves had higher levels of TPO Ab, with a positive trend of this antibody overtime in comparison to other quartiles, indicating that this group may be at a higher risk of hypothyroidism over time.

Protective role of vitamin D status against COVID-19: a mini-review.

An outbreak of pneumonia caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is called COVID-19 and has led to a pandemic worldwide. It is reasonable to investigate and control factors affecting disease severity and mortality. The relation between vitamin D and viral pneumonia has been previously reported. Vitamin D deficiency is common and may increase hospital admission and mortality rate in patients with COVID-19. This mini-review examines the pathways that show the association between vitamin D and COVID-19. On the other hand, it deals with the available evidence related to the relationship between vitamin D deficiency and the effect of vitamin D supplementation on the prevalence, severity, and mortality of COVID-19. Also, we described the pathophysiology of the organs' involvement in COVID-19 and the effect of vitamin D on these outcomes. Vitamin D strengthens the innate and adaptive immune system, modulates immune responses, prevents lung and cardiovascular system damage, and reduces thrombotic events. Vitamin D exerts these effects in several pathways. Vitamin D prevents virus entry and replication by maintaining the integrity of the body's physical barrier. Vitamin D reduces the damage to vital organs and thrombotic events by increasing the level of Angiotensin-converting enzyme 2 (ACE2), nitric oxide, and antioxidants or by reducing inflammatory cytokines and free radicals. Sufficient vitamin D may be reduced morbidity and mortality due to COVID-19. However, this issue should be investigated and confirmed by further research in the future.

The role of electrolyte imbalances in predicting the severity of COVID-19 in the hospitalized patients: a cross-sectional study.

Coronavirus disease 2019 (COVID-19) can be fatal in severe cases. Accordingly, predicting the severity and prognosis of the disease is valuable. This study examined the role of electrolyte imbalances in predicting the severity of COVID-19. In this cross-sectional study, 169 hospitalized patients with COVID-19 were included and categorized into three groups based on the severity of the disease (moderate, severe, and critical). Serum levels of electrolytes (calcium [Ca], phosphorus [P], sodium [Na], potassium [k], and magnesium [Mg]), inflammatory markers (D-dimer, C-reactive protein [CRP], ferritin, and lactate dehydrogenase [LDH]), and 25OHVitamin D were measured. The mean age of patients was 53 years, and 54% were male. They had moderate, severe, and critical illnesses in 22%, 47%, and 31%, respectively. CRP, D-dimer, and ferritin increased with the severity of the disease. The lower median values of Mg, Na, 25OHVitamin D, Ca, LDH, and higher median lymphocyte counts were observed in the moderate vs. the severe group (P < 0.05). These parameters have acceptable sensitivity and specificity at the suggested cut-off level to discriminate the moderate and critical cases. Serum parameters introduced in this study are appropriate for differentiating between critical and moderate cases. The electrolyte imbalance can predict critical patients.

Evaluating Possible Mechanisms Linking Obesity to COVID-19: a Narrative Review.

Currently, pneumonia caused by the coronavirus disease 2019 (COVID-19) is a pandemic. To date, there is no specific antiviral treatment for the disease, and universal access to the vaccine is a serious challenge. Some observational studies have shown that COVID-19 is more common in countries with a high prevalence of obesity and that people with COVID-19 have a higher body mass index. In these studies, obesity increased the risk of disease, as well as its severity and mortality. This study aimed to review the mechanisms that link obesity to COVID-19.

National Research Institute of Tuberculosis and Lung Disease (NRITLD) Protocol for the Treatment of Patients with COVID-19.

More than a year after the onset of the coronavirus disease pandemic in 2019, the disease remains a major global health issue. During this time, health organizations worldwide have tried to provide integrated treatment guidelines to control coronavirus disease 2019 (COVID-19) at different levels. However, due to the novel nature of the disease and the emergence of new variants, medical teams' updating medical information and drug prescribing guidelines should be given special attention. This version is an updated instruction of the National Research Institute of Tuberculosis and Lung Disease (NRITLD) in collaboration with a group of specialists from Masih Daneshvari Hospital in Tehran, Iran, which is provided to update the information of caring clinicians for the treatment and care of COVID-19 hospitalized patients.

Dramatic response of aneurysmal bone cyst to denosumab: Case report and literature review.

Denosumab, a monoclonal antibody that specifically targets cytokine receptor activator of nuclear factor-kappa B ligand (RANKL), is a potentially viable option in resistant aneurysmal bone cysts.

The relationship between serum 25-hydroxyvitamin D levels and the severity of COVID-19 disease and its mortality.

Supplemental vitamin D can reduce the risk and mortality of viral pneumonia. The relationship between 25 hydroxyvitamin D [25(OH)D] levels and the severity and mortality of Coronavirus disease 2019 (COVID-19) was evaluated. In this cross-sectional study, the admitted patients with COVID-19 were categorized as mild, moderate, severe, and critical based on clinical and radiologic characteristics. Calcium, phosphorus, albumin, creatinine, and serum 25(OH)D were measured and their correlation with the severity of disease and mortality were analyzed. During 2 months, 508 patients (442 patients in general wards and 66 patients in the intensive care unit (ICU)) were included. The participants were 56 ± 17 years old (52% male, 37% with comorbidity). Concerning severity, 13%, 42%, 36%, and 9% had mild, moderate, severe, and critical diseases, respectively. The mortality rate was 10.8%. Admission to ICU, severity of disease and mortality decreased significantly across quartiles of 25(OH)D. According to multivariate logistic regression analysis, disease mortality had a positive correlation with age and had a negative correlation with the serum level of 25(OH)D, calcium, and albumin. In hospitalized patients with COVID-19, low 25(OH)D was associated with severe disease and increased ICU admission and mortality rate.

The relationship between QT interval indices with cardiac autonomic neuropathy in diabetic patients: a case control study.

BACKGROUND: Long QT interval (QT) and abnormal QT dispersion (QTd) are associated with sudden death. The relationship between cardiac autonomic neuropathy (CAN) and QT indices in type 2 diabetic patients were investigated. METHODS: Totally 130 diabetic subjects (mean age 50.87 ± 13.9 years) were included (70 individuals with and 60 individuals without CAN). All participants had sinus cardiac rhythm. The patients who had diseases or take drugs that cause orthostatic hypotension (OH), cardiac arrhythmia and QT prolongation were excluded. After interview and examination, standard and continuous ECG was taken in supine position with deep breathing and standing up position. CAN diagnosis was based on Ewing's tests. QT, QT corrected (QTc), minimum QT (QT min), maximum QT (QT max) and mean ± SD of QT (QT mean) and QTd were assessed from standard ECG. QTc was calculated by Bazett's formula from V2 lead. QTc > 440 ms in men and QTc > 460 ms in women and QTd > 80 ms were considered abnormal. RESULTS: In patients with CAN, 21.5% were symptomatic. The prevalence of abnormal QTc and QTd was 11.3% and 28.7%, respectively. There was no significant difference between the patients with or without CAN in terms of long QTc and abnormal QTd. However, the mean ± SD of QT max, QT mean and QTd was higher in the patients with CAN (P value < 0.03). The used cut points for QTc and QTd have high specificity (79% for both) and low sensitivity (30% and 37%, respectively). To use QTc and QTd as screening test for CAN in T2DM patients, the cutoff points 380 and 550 ms are suggested, respectively. CONCLUSION: The prevalence of asymptomatic CAN was 3.7 times that of symptomatic CAN. In patients with CAN the QT max, QT mean and QTd were higher than those without CAN. There was no association between CAN and long QTc and abnormal QTd.

Clinical Manifestations of Patients with Coronavirus Disease 2019 (COVID-19) in a Referral Center in Iran.

BACKGROUND: Following the recent epidemic of coronavirus disease 2019 (COVID-19) in Wuhan, China, a novel betacoronavirus was isolated from two patients in Iran on February 19, 2020. In this study, we aimed to determine the clinical manifestations and outcomes of the first confirmed cases of COVID-19 infection (n=127). MATERIALS AND METHODS: This prospective study was conducted on all COVID-19-suspected cases, admitted to Masih Daneshvari Hospital (a designated hospital for COVID-19), Tehran, Iran, since February 19, 2020. All patients were tested for COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR) assay. Data of confirmed cases, including demographic characteristics, clinical features, and outcomes, were collected and compared between three groups of patients, requiring different types of admission (requiring ICU admission, admission to the general ward, and transfer to ICU). RESULTS: Of 412 suspected cases, with the mean age of 54.1 years (SD=13.4), 127 (31%) were positive for COVID-19. Following the patients' first visit to the clinic, 115 cases were admitted to the general ward, while ten patients required ICU admission. Due to clinical deterioration in the condition of 25 patients (out of 115 patients), ICU admission was essential. Based on the results, the baseline characteristics of the groups were similar. Patients requiring ICU admission were more likely to have multiorgan involvement (liver involvement, P<0.001; renal involvement, P<0.001; and cardiac involvement, P=0.02), low O2 saturation (P<0.001), and lymphopenia (P=0.05). During hospital admission, 21 (16.5%) patients died, while the rest (83.5%) were discharged and followed-up until March 26, 2020. Also, the survival rate of patients, who received immunoglobulin, was higher than other patients (60.87% vs. 39.13%). CONCLUSION: The mortality rate of COVID-19 patients was considerable in our study. Based on the present results, this infection can cause multiorgan damage. Therefore, intensive monitoring of these patients needs to be considered.

The association between cardiac autonomic neuropathy and diabetes control.

Introduction: Cardiac autonomic neuropathy (CAN) is one of major complications of diabetes mellitus (DM) that increases the risk of cardiovascular disorders, abnormal ventricular depolarization with poor prognosis as well as increased mortality and morbidity. Indeed, CAN has close relation with blood glucose level in diabetic patients. We investigated the relation of CAN with diabetes control. Materials and methods: Totally, 115 diabetic patients (mean age 50.87±13.90 years old; 78 females) underwent study. All patients had DM and cardiac sinus rhythm. Nobody had sickness affecting cardiac rhythm and blood pressure. In addition, they did not take drugs that had effect on blood pressure, cardiac rhythm, and QT interval. Forty-six patients had tight and 69 patients had uncontrolled DM according to American Diabetes Association (ADA) criteria. The CAN was assessed based on heart rate variation during physical examination (at rest tachycardia and orthostatic hypotension) and standard Ewing's tests (deep-breathing and laying-to-standing tests) with bedside continuous ECG recording. The P-value <0.05 is considered significant. Results: Seventy-five patients (65.2%) had CAN. In patients with CAN, 13.9% were symptomatic and 51.3% were asymptomatic. Resting tachycardia and hypotension were found in 5.2%, 8.7% of patients, respectively. Abnormal deep-breathing and laying-to-standing tests were found in 73% and 71.3% of asymptomatic patients, respectively. CAN was more prevalence at uncontrolled DM (67.3% vs 63.7%) but the difference was not significant. The prevalence of CAN had direct association with duration of DM in both tight and uncontrolled groups (P<0.05). The mean of age, sex, and type of treatment had no association with CAN prevalence. Conclusion: The prevalence of CAN, especially asymptomatic type, was high. Its prevalence was increased with prolonged duration of DM. But we did not find any relationship between CAN and glycemic control level.

Association between serum concentration of 25-hydroxyvitamin D and community-acquired pneumonia: a case-control study.

BACKGROUND: Community-acquired pneumonia (CAP) is a common disease with significant morbidity and mortality. There is evidence that vitamin D deficiency can be associated with infectious diseases. The aim of this study was to compare the levels of vitamin D between patients with CAP and healthy controls. METHODS: In a case-control study on 73 patients with CAP and 76 healthy controls, the serum concentration of 25-hydroxyvitamin D (25[OH]D) was measured. Severity and outcomes of disease and also duration of hospital stay were compared in patients with different levels of 25(OH)D. The severity of CAP was assessed using the CURB-65 score (confusion, uremia, respiratory rate, low blood pressure, age ≥65 years) and was also reflected by the length of hospital stay, admission to intensive care unit (ICU), and 30-day mortality. RESULTS: In total, 81.2% of the study population had vitamin D levels <30 ng/dL. The risk of pneumonia among subjects with deficient vitamin D levels was 3.69 (95% CI: 1.46, 9.31) times of those with sufficient vitamin D level (P=0.006). Prevalence of severe deficiency of vitamin D in scores three and four of CURB-65 (59.38%), was far more than scores one and two (31.71%). Also, results indicated patients with severe deficiency had a higher risk for ICU admission, 30-day mortality, and longer hospitalization stay, but these were not statistically significant. CONCLUSION: According to findings, a low level of 25(OH)D is associated with a higher incidence of CAP and more severe disease. It is recommended to pay more attention to vitamin D deficiency in infectious diseases, particularly in CAP patients.

Short-term cohort study on sensorineural hearing changes in head and neck radiotherapy.

The aim of this study was to investigate the risk of sensorineural hearing loss (SNHL) and the relationship between SNHL and radiation dose to the cochlea and frequency range of hearing loss in patients with head and neck cancer. Pure tone audiometry at 250-12,000 Hz was performed on 29 patients diagnosed with head and neck tumours who were treated with 3-dimensional conformal radiation therapy and followed up for 6 months. Paired t test indicated that the mean air conduction threshold before and after radiotherapy was significantly different (paired t test, p < 0.001). SNHL was observed in 15 patients (51 %) according to CTCAE. SNHL increased to 77 % in patients who had received at least five concurrent cisplatin cycles. There was an increased risk of SNHL for ears receiving a mean dose of 5000 cGy compared to those receiving <5000 cGy. SNHL was more severe at higher frequencies of pure tone audiometry in patients with cisplatin-based chemoradiation. The ototoxicity effect of radiation and cisplatin must be considered in the treatment of head and neck tumours. Increasing the dose of cisplatin, radiation dose of cochlea and follow-up interval time may result in increasing severity and frequency of hearing loss incidences. However, characteristic of radiation-induced SNHL seems to be different from chemoradiation-induced SNHL.

Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy.

PURPOSE: To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. METHODS AND MATERIALS: Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/ß = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. RESULTS: Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy. CONCLUSIONS: The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication.

Thyroid autoimmunity role in the evolution of endemic goiter in rural area, Fars, Iran.

BACKGROUND: WHO reports indicate no iodine insufficiency in Iran, however, goiter is still endemic in Fars Province. This study evaluates the role of thyroid autoimmunity in the evolution of endemic goiter. METHODS: A total of 516 permanent residents of Akbarabad County of the Kavar area in Fars Province, Iran were selected by simple random sampling. Patients with thyroid malignancy and dysfunction, and those who consumed drugs affecting thyroid function were excluded. After signing a written consent form and undergoing a thyroid examination, 5 cc of blood were drawn to measure free T3 and T4 (RIA), TSH (IRMA), and anti-thyroid peroxidase (competitive RIA) levels. Moreover, samples of 50 cc morning urine were collected for the measurement of urinary iodine excretion (UIE; chloridric acid digestion). Data were analyzed by SPSS (version 13). P<0.05 was significant. RESULTS: The prevalence of goiter was 38.4% by WHO classification. The prevalence of children with UIE 2-4.9 µg/dL was 5.8%, which indicated sufficient iodine intake. Goiter was more prevalent in females, as well as in patients with positive anti-TPO or higher TSH titers (P<0.01). The prevalence of positive anti-TPO was higher in goiterous patients than healthy persons (P=0.002), which increased with an increase in age, grade of thyromegaly or TSH (P<0.02). Regression analysis showed the odds ratio for diagnosing goiter in females was 2.4 (P<0.001), in those with positive anti-TPO it was 1.87 (P=0.03) and in those with TSH>5.2 mIU/mL the odds ratio was 2.74 (P=0.01). In adolescents compared to children the odds ratio was 0.36 (P=0.01) and the odds ratio in adults to children was 0.33 (P=0.001). CONCLUSION: This study indicates that despite normal UIE, goiter is endemic in Akbarabad County. Some degree of goiter endemicity may be due to thyroid autoimmunity.