A Rare Case of Pulmonary Hypertension, Misdiagnosed as Interstitial Lung Disease: Pulmonary Capillary Hemangiomatosis.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension. We reported a histologically confirmed PCH in a 42-yr-old lady. She presented a progressive dyspnea and cough after an upper respiratory tract infection. She had a leukocytosis and elevated ESR with negative collagen vascular laboratory results. Her chest imaging revealed mediastinal lymphadenopathy with bilateral ground glass opacities with increased interstitial septal thickening in lung parenchyma. Patient echocardiography showed severe right ventricular dilatation with a measured systolic pulmonary arterial pressure of about 105mmHg. Right heart catheterization revealed a mean pulmonary arterial pressure on 30 mmHg with a pulmonary capillary wedge pressure of about 7 mmHg. After starting anti PH treatment, the patient suffered a pulmonary edema and due to abnormal patient response to anti-PH therapies and radiologic findings. Finally, open lung biopsy was performed and showed features of pulmonary capillary hemangiomatosis.

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.

Possibility of Applying Heart Rate Variability as a Screening Method to High-Risk Obstructive Sleep Apnea Patients.

Background: Altered heart rate variability (HRV) has been associated with a number of disorders affecting autonomic tone, including recent myocardial infarction, congestive heart failure, and diabetic neuropathy. Furthermore, obstructive sleep apnea (OSA) has been shown to be associated with characteristic disturbances in heart rhythm. In this study, using HRV frequency analysis, an attempt has been made to diagnose or possibly diagnose OSA. Materials and Methods: Using Somnologica version 3.3.1 software (Medcare-Embla), polysomnographic recordings were done. Electrocardiographic signals were digitalized with a sampling rate of 250 Hz. Using the HRV analysis report of this software, low-frequency (LF) and high- frequency (HF) information and LF to HF ratio (LF/HF) were obtained at 5-min intervals, then at cutting points 30, 35, 40, 45, and 50, which indicate the intensity of the apnea and hypopnea index (AHI), were analyzed with mean and standard deviation of HRV frequencies. Results: According to the results reported in this study, comparison of mild, moderate, and severe cases led to no significant differences, while frequency-domain analysis displayed significant LF/HF increase in more severe AHI cases. This can probably be applied in screening high-risk patients, reducing the application of PSG in high probable cases, and providing an estimate of prognosis of potentials patients for the physicians. Conclusions: In the study of frequency-domain analysis, LF/HF increases in more severe AHI cases. These can probably be applied in screening high-risk patients, reducing the application of PSG in high probable cases.

Prognostic Value of Platelet to Lymphocyte Ratio (PLR) and Neutrophil to Lymphocyte Ratio (NLR) in Patients with Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a hemodynamic and pathophysiological disease defined by a mean pulmonary artery pressure of ≥20 mm Hg. Pulmonary hypertension severity and prognosis play an essential role in the management of these patients. The aim of this study was to evaluate the prognostic value of platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) in patients with PH referred to Masih Daneshvari Hospital, Tehran, Iran. Materials and Methods: A total of 61 patients with PH referred to Masih Daneshvari Hospital in Tehran were enrolled. Patients' information such as age, sex, type of PH, echocardiographic data, and blood cell count, including platelet, lymphocyte, and neutrophil count, hemoglobin, and RDW, were collected in each follow-up. Results: Out of 61 patients with PH, 27 (44.3%) were male, and 34 (55.7%) were female. The mean age of the patients was 43.19 ± 2.25 years. Our results showed that during hospitalization, PLR decreased from 13.2 to 9.7, and NLR also decreased from 4.49 to 3.08. Neither PLR nor NLR was associated with gender. However, both PLR and NLR showed a significant difference between deceased vs. discharged patients and were significantly lower in the patients who died. Conclusion: Both PLR and NLR decreased during hospitalization in patients with PH, and this decrease was greater in the patients who died, suggesting these indicators as potential prognostic markers for the disease.

Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm. Objectives: To elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity. Methods: We determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran. Results: Serum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR. Conclusions: The study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.

The effect of buprenorphine vs methadone on sleep breathing disorders.

Opioids are used widely as analgesics and can play an important role in agonist maintenance therapy for opium dependence. Despite their benefits, the negative effects on the respiratory system remain an important side effect to be considered. Ataxic breathing, obstructive sleep apnea, and most of all central sleep apnea are among these concerns. Obstructive sleep apnea leads to various metabolic, cardiovascular, cognitive, and mental side effects and may result in abrupt mortality. Buprenorphine is a semisynthetic opioid, a partial mu-opioid agonist with limited respiratory toxicity preferably used by these patients, as it is accompanied by significantly lower risk factors in the development of obstructive and central sleep apnea. In this manuscript, the case of a patient is reported who underwent methadone maintenance therapy which was shifted to buprenorphine in order to observe possible changes in sleep-related breathing disorders. The results of this study indicate a reduction in these problems through the desaturation and apnea hypopnea index of methadone substituted by buprenorphine while no change in sleepiness was observed.

No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial.

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P < 0.001). No significant differences were observed in the other outcomes. This study showed that corticosteroid administration had no clinical benefit in patients with COVID-19-induced mild to moderate ARDS.

Decreased neutrophil-mediated bacterial killing in COVID-19 patients.

The coronavirus disease COVID-19 was first described in December 2019. The peripheral blood of COVID-19 patients have increased numbers of neutrophils which are important in controlling the bacterial infections observed in COVID-19. We sought to evaluate the cytotoxic capacity of neutrophils in COVID-19 patients. 34 confirmed COVID-19 patients (29 severe, five mild disease), and nine healthy controls were recruited from the Masih Daneshvari Hospital (Tehran, Iran) from March to May 2020. Polymorphonuclear (PMN) cells were isolated from whole blood and incubated with green fluorescent protein (GFP)-labelled methicillin-resistant Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Bacterial growth was determined by measuring the florescence of co-cultures of bacteria and neutrophils and reported as the lag time before exponential growth. The number of viable bacteria was determined after 70 hours as colony-forming units (CFU). The immunophenotype of tested cells was evaluated by flow cytometry. Isolated neutrophils have higher surface expression of CD16 and CD62L with negative markers for PMN-MDSC. Bacterial growth in the presence of SA (22 ± 0.9 versus 9.2 ± 0.5 h, P < .01) and PA (12.4 ± 0.6 versus 4.5 ± 0.22, P < .01) was significantly reduced in COVID-19 patients. After 70 h incubation of PMN with bacteria (SA and PA), CFUs were significant increased in COVID-19 patients SA (2.6 ± 0.09 × 108 CFU/mL-severe patients and 1.4 ± 0.06 × 108 CFU/mL-mild patients, P < .001) and PA (2.2 ± 0.09 × 109 CFU/mL-severe patients and 1.6 ± 0.03 × 109 CFU/mL-mild patients, P < .001). Gentamycin proliferation assays confirmed the presence of intracellular bacteria. Reduced bacterial killing by neutrophils from COVID-19 patients may be responsible for the high bacterial yield seen in these patients.

Plasmapheresis reduces cytokine and immune cell levels in COVID-19 patients with acute respiratory distress syndrome (ARDS).

BACKGROUND: In December 2019, pneumonia associated with a novel coronavirus (COVID-19) was reported in Wuhan, China. Acute respiratory distress syndrome (ARDS) is the most frequently observed complication in COVID-19 patients with high mortality rates. OBJECTIVE OF STUDY: To observe the clinical effect of plasmapheresis on excessive inflammatory reaction and immune features in patients with severe COVID-19 at risk of ARDS. MATERIALS AND METHODS: In this single-center study, we included 15 confirmed cases of COVID-19 at Masih Daneshvari Hospital, in March 2020 in Tehran, Iran. COVID-19 cases were confirmed by RT-PCR and CT imaging according to WHO guidelines. Plasmapheresis was performed to alleviate cytokine-induced ARDS. The improvement in oxygen delivery (PaO2/FiO2), total number of T cells, liver enzymes, acute reaction proteins, TNF-α and IL-6 levels were evaluated. RESULTS: Inflammatory cytokine levels (TNF-α, IL-6), and acute phase reaction proteins including ferritin and CRP were high before plasmapheresis. After plasmapheresis, the levels of PaO2/FiO2, acute phase reactants, inflammatory mediators, liver enzymes and bilirubin were significantly reduced within a week (p < 0.05). In contrast, although the number of T helper cells decreased immediately after plasmapheresis, they rose to above baseline levels after 1 week. Nine out of fifteen patients on non-invasive positive-pressure ventilation (NIPPV) survived whilst the six patients undergoing invasive mechanical ventilation (IMV) died. CONCLUSION: Our data suggests that plasmapheresis improves systemic cytokine and immune responses in patients with severe COVID-19 who do not undergo IMV. Further controlled studies are required to explore the efficacy of plasmapheresis treatment in patients with COVID-19.

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.

Neurological Manifestations of COVID-19: A Case Report.

A novel coronavirus disease (COVID-19) was reported in Wuhan, China in December 2019 and spread rapidly around the world, causing high rates of mortality and morbidity. This disease is known for its respiratory manifestations. Also, there have been several reports of neurological involvement in patients with COVID-19. In this study, we present a 55-year-old Iranian male patient, who was referred from another medical center with a decreased level of consciousness. Upon admission, only respiratory signs of COVID-19 were observed, but later, some neurological manifestations were also observed, such as an alteration in mental status, disorientation, stupor, and finally coma. In radiological studies, a hemorrhagic encephalopathy pattern was detected. Despite improved oxygenation and alleviation of respiratory symptoms with antiviral and anti-inflammatory therapies, cerebral injuries progressed, and the patient died due to severe brain damage.

Sleep Disorders and Mental Health in Menopausal Women in Tehran.

BACKGROUND: Sleep complaints are common problems in the general population and insomnia and sleep disorders place significant economic and social burdens on the community. Postmenopausal women are 2.6 to 3.5 times more likely to develop obstructive sleep apnea (OSA) compared to non-menopausal women. In this study, we evaluated sleep disorders and mental health in postmenopausal women. MATERIALS AND METHODS: This study was a descriptive cross-sectional study and the samples were selected from postmenopausal women above 50 years who had participated in a survey entitled, "Evaluation of Sleep Disorders among Adults in Tehran" in 2017. Cluster sampling method was applied with proportional allocation. A total of 4021 samples were collected, 2075 of which belonged to women. In addition, 174 out of 2075 samples were related to postmenopausal women over the age of 50. The data were analyzed using the statistical package IBM SPSS version 22.0. P-values less than 0.05 were considered significant. RESULTS: In this study, 118 (67.8%) women had insomnia for less than three months, and 23 (13.2%) women had insomnia for more than three months. The prevalence of STOPBANG parameters in this group of postmenopausal women was 37% and significantly related to Body mass index (BMI) and neck circumference at P < 0.001 and 0.006, respectively. There was no significant relationship between social dysfunction and insomnia. However, anxiety in General Health Questionnaire (GHQ) was significantly associated with insomnia, sleepiness, sadness, and irritability. CONCLUSION: Our results indicate that the impact of insomnia symptoms, OSA comorbidity and mental disorders could extend far beyond. The use of urgent health care and quality of life issues is essential for long-term mental and physical well-being; if there is no treatment in the menopause population, there will be serious mental and physical complications.

Blood Purification Techniques, Inflammatory Mediators and Mortality in COVID-19 Patients.

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

Clinical Features and Outcomes of ICU Patients with COVID-19 Infection in Tehran, Iran: a Single-Centered Retrospective Cohort Study.

BACKGROUND: The clinical characteristics of the novel coronavirus disease (COVID-19) were diverse and unspecific. Here, we identified the associated factors with surviving of COVID-19 ICU patients based on the clinical characteristics of patients admitted to one of the Corona Centre Hospitals of Iran. MATERIALS AND METHODS: This cohort study was performed retrospectively from February to June 2020 on 133 COVID-19 patients admitted to 4 intensive care units of Masih Daneshvari Hospital in Tehran, Iran. Demographic, medical, clinical manifestation at admission, laboratory parameters and outcome data were obtained from medical records. Also the SOFA and APACHE II scores were calculated. All data were analyzed using SPSS (version 23, IBM Corp.) software. RESULTS: The median (IQR) age of the patients was 62.0 (54.0-72.0) years in total. RT-PCR of throat swab SARS-CoV-2 in 80 patients (60.2%) was positive. Total mortality rate was 57.9 percent (77 patients). Dyspnea, hypertension and chronic pulmonary diseases were significantly common in non-survivors than survivors (p<0.05). Both SOFA and APACHE II scores were significantly higher in the non-survivors (p<0.05). Also other significant differences were observed in other parameters of the study. CONCLUSION: The mortality rate of COVID-19 patients admitted to ICU is generally high. Dyspnea as initial presentation and comorbidity, especially hypertension and pulmonary diseases, may be associated with higher risk of severe disease and consequent mortality rate. Also, higher SOFA and APACHE II scores could indicate higher mortality in patients admitted to ICU.

Beneficial Outcomes of Early Tracheostomy in Patients Requiring Prolonged Mechanical Ventilation.

BACKGROUND: Considering that tracheostomy is being done for huge amount of critically ill patients, the ideal time for this procedure is still controversial among different intensive care units (ICU). MATERIALS AND METHODS: 70 intubated patients were included in our study which was sorted into two subgroups: half of our patients received an early tracheostomy (ET) within 1-10 days post intubation and the rest received late tracheostomy (LT) within 11-21 days after getting intubated. RESULTS: 61.9% of the study population was male and the mean age was of 54 + 10.5 years. ET group mean Mechanical Ventilation (MV) duration was 8.11±4.9 days and was 16.3 ± 6.01 in the LT group (p<0.05) with a mean sedation duration of 6.1 ± 4.4 vs. 12.0 ± 6.5 (ET vs. LT) (p<0.05). Mean time of weaning process from ventilator was 2.7 ±2.3 for ET group and 5.5 ± 5.0 for LT group (p<0.05). The Mean ICU stay was 18.8 ± 2.2 in the ET group, and 22.1 ± 4.1 in the LT group (p: 0.98) at the same time. Length of stay at hospital for two group of patients did not show a meaningful difference (p= 0.279). CONCLUSION: Early tracheostomy decreases duration of mechanical ventilation and sedation use and more rapid weaning process in those patients who will require mechanical ventilation. Our findings revealed that tracheostomy timing has no significant impact on rate of hospital mortality and LOS at ICU and hospital.

The Prevalence and Outcome of Intensive Care Unit Acquired Weakness (ICUAW).

BACKGROUND: Intensive care unit acquired weakness (ICUAW) is a known complication in ICU patients, especially in those with severe underlying diseases. The cause and pathogenesis of ICUAW are still unknown. This study examined the incidence rate of ICUAW in intensive care units (ICUs) of the Masih-Daneshvari Hospital. MATERIALS AND METHODS: This descriptive-comparative study was conducted on 160 patients admitted in the ICUs, including an acute respiratory infectious ICU (TB-ICU) and medical ICU. The total number of patients was 80 in each of the ICUs. Demographic information was obtained from the patients after the initial examination and Medical Research Council (MRC) score was done on daily basis. EMG was performed on the 2nd and 8th days of the admission. ICUAW diagnosis was used in cases with MRC scores under 48. RESULTS: Among the patients, 68.6% were male and the mean age was 59.13±18. 68 years. The final outcomes were 48.4% mortality and 51.6% discharge, which were 41% and 59% in the TB-ICU and 56.7% and 43.3% in the medical ICU, respectively. By defining electromyography as the gold standard, the sensitivity and specificity of ICUAW diagnosis based on the MRC score definition were about 70% and 83%, respectively. The comparison ICUAW patients in the two ICUs in terms of mortality showed no significant difference between them. CONCLUSION: It is concluded that nearly half of ICU-admitted patients develop ICUAW that causes a higher mortality rate. Therefore, new plans should be developed to reduce the rate of ICUAW and subsequent death, as well as other possible morbidities.

The effect of acetazolamide on the improvement of central apnea caused by abusing opioid drugs in the clinical trial.

PURPOSE: Acetazolamide is utilized as a treatment which falls effective in treating some type of CSA. Hence, it might be effective as far as opium addicts who suffer from CSA are concerned. MATERIALS AND METHOD: The current study was a double-blind, placebo-controlled, cross-over study ( clinicalTrials.gov ID: NCT02371473). The whole procedures were identical for both placebo and acetazolamide phases of clinical research. There were 14 CSA more than 5/h and more than 50% of apnea-hypopnea index (AHI). Out of these 14 patients, 10 volunteered to participate in the study. Fast Fourier transformation was used to separate heart rate variability (HRV) into its component VLF (very low frequency band), LF (low frequency band), and HF (high frequency band) rhythms that operate within different frequency ranges. RESULT: There are significant results in terms of decreased mix apnea and central apnea together due to acetazolamide compared with placebo (P < 0.023). Time of SatO2 < 90% is decreased as well (P < 0.1). There is also decrease of SDNN and NN50 after treatment with acetazolamide respectively (P < 0.001). Regarding fast Fourier transformation, there is increase of pHF and decrease of pLF after acetazolamide treatment (P < 0.001). CONCLUSION: Acetazolamide seems to be effective in improving oxygenation and a decrease of mixed and central apnea events together. In HRV analysis section, LF power has decreased significantly, which may more likely improve prognosis of the patients.

Correction to: Exhaled nitric oxide is not a biomarker for idiopathic pulmonary arterial hypertension or for treatment efficacy.

Following publication of the original article [1], the authors flagged that name of the author 'Batoul Khoundabi' had been provided with an incorrect spelling: 'Batoutl' was given in place of 'Batoul'.