Sarcopenia in pulmonary diseases is associated with elevated sarcoplasmic reticulum stress and myonuclear disorganization.

Chronic obstructive pulmonary disease (COPD) is frequently associated with age-related muscle loss or sarcopenia. However, the exact molecular mechanism of muscle loss in COPD remains elusive. We investigated the association of chronic dysregulation of sarcoplasmic reticulum (SR) protein homeostasis (a condition called SR stress) and myonuclear disorganization with sarcopenia in patients with COPD. Markers of SR stress and their downstream consequences, including apoptosis and inflammation, were upregulated in patients with COPD. The maximal SR Ca2+ ATPase (SERCA) activity was significantly reduced in advanced COPD as compared to healthy controls. Single muscle fiber diameter and cytoplasmic domain per myonucleus were significantly smaller in patients with advanced COPD than in healthy controls. Increased disruption of myonuclear organization was found in the COPD patients as compared to healthy controls. These changes in SR dysfunction were accompanied by elevated global levels of oxidative stress, including lipid peroxidation and mitochondrial reactive oxygen species (ROS) production. Altogether, our data suggest that muscle weakness in advanced COPD is in part associated with the disruption of SR protein and calcium homeostasis and their pathological consequences.

Relationship of Haptoglobin Phenotypes With Sarcopaenia in Patients With Congestive Heart Failure.

BACKGROUND: Systemic inflammation in patients with chronic heart failure (CHF) contributes to age-related muscle loss or sarcopaenia. However, the relationship of plasma haptoglobin (Hp), an acute-phase reactant, with muscle and physical health in CHF is unknown. METHODS: This study investigated the associations of plasma haptoglobin levels and phenotypes with handgrip strength (HGS), appendicular skeletal muscle index (ASMI) and physical capacity in healthy controls (n=67) and CHF patients (n=61) aged 55-73 years. RESULTS: Patients with CHF had higher plasma Hp levels and higher proportions of Hp2-2 phenotype when compared with healthy controls. Plasma Hp2-1 and Hp2-2 levels were negatively associated with HGS and ASMI in healthy controls and CHF (both p<0.05). A negative association of plasma Hp2-2 with gait speed and plasma Hp2-1 with daily steps count was also found in CHF (p<0.05). Patients with Hp2 phenotype showed higher expressions of inflammation and oxidative stress markers, as well as low scores on quality of life parameters. CONCLUSIONS: Circulating Hp may be a valuable biomarker for assessing muscle health and physical capacity in CHF.

FREQUENCY OF DIFFERENT VALVULAR LESIONS OF RHEUMATIC HEART DISEASE PRESENTING TO A TERTIARY CARE HOSPITAL.

BACKGROUND: Rheumatic Hearth Disease (RHD) is still prevalent in our country and a great source of morbidity. This study was done with an objective to determine relative frequency of different valvular lesions of RHD presenting in a tertiary care hospital. METHODS: This cross sectional study was conducted at the Cardiology Department of Hayatabad Medical Complex, Peshawar. A total of 171 cases of RHD were included through consecutive sampling technique. RESULTS: There were 64.33% females. Mean age was 25.6 +/- 6.95 years ranging from 15 to 40 years. The different percentage of valvular lesions in RHD were MR (59.06%), MS (46.78%), AR (43.85%) and mixed lesions (38.59%). CONCLUSION: Rheumatic heart disease is a very common disease in our community and mitral regurgitation is a predominant lesion at presentation Females are usually affected more than males.

3D ultrasound-augmented image guidance for surgery of high-grade gliomas - A quantitative analysis focused on the extent of resection.

Background: We have retrospectively reviewed our series of brain tumor patients operated on using 3D IntraOperative UltraSound (IOUS) to report technical advantages and areas of improvement. Methods: Clinical and radiological data of patients with a diagnosis of high-grade glioma IV operated with and without IOUS were retrieved and analyzed. Results: We have found 391 patients operated using IOUS coupled with neuronavigation and 257 using neuronavigation standalone. We have selected a pool of 60 patients with a diagnosis of GlioBlastoma (GB), comparing two equally sized groups operated with and without IOUS, respectively. The average extent of resection (EOR) in the IOUS group was 93%, while in the control group, it was 80%. IOUS was significantly associated with improved EOR (P < 0.0004), even when accounting for other factors affecting EOR. The average overall survival (OS) was 13.4 months, and the average progression-free survival (PFS) was 7.4 months. The Cox proportional hazard model showed an advantage in OS on patients operated using the IOUS. No statistically significant effect was observed on PFS. Conclusion: Intraoperative ultrasound coupled with image guidance is associated with an improved EOR and possibly an improved OS. While we are aware of several limitations related to the present analysis, these data support the routine use of IOUS as a safe and reliable technology. Larger, prospective series with updated IOUS technology are desirable to verify the accuracy of these results.

A multistrain probiotic reduces sarcopenia by modulating Wnt signaling biomarkers in patients with chronic heart failure.

BACKGROUND: The muscle decline due to aging, called sarcopenia and functional compromise, are common occurrences in patients with chronic heart failure (CHF). Intestinal dysbiosis and the alterations in Wnt signaling may partly account for these findings. We investigated the effects of a multistrain probiotic on Wnt signaling biomarkers and their associations with sarcopenia and functional capacity in CHF patients. METHODS: The CHF patients were randomized into placebo (n = 48) and probiotic (n = 44) groups for 12 weeks. We measured circulating markers of intestinal permeability (zonulin) and Wnt signaling (dickkopf-1, Dkk-1; dickkopf-3, Dkk-3), and sterol regulatory element-binding protein-1 (SREBP1), handgrip strength (HGS), and short physical performance battery (SPPB) scores at baseline and after probiotics treatment. RESULTS: Probiotics treatment improved HGS, gait speed, and plasma Dkk-1, and reduced plasma zonulin, Dkk-3, and SREBP1 in CHF patients (all p < 0.05). Among sarcopenia indexes, HGS showed robust correlations with the three Wnt biomarkers (all p < 0.05). Probiotic treatment also improved the SPPB scores in CHF patients, which were strongly correlated with Dkk-3, followed by Dkk-1, and SREBP1 (all p < 0.05). SREBP1 and Dkk-3 demonstrated significant potential in diagnosing sarcopenia in CHF patients. Probiotics also reduced the plasma markers of inflammation and oxidative stress in CHF patients. CONCLUSION: The multistrain probiotic reduces sarcopenia and improves functional capacity in CHF patients by modulating Wnt signaling.

A Prospective Observational Study Comparing the Efficacy and Safety of Duloxetine and Pregabalin in Diabetic Peripheral Neuropathic Pain.

Background and aims Peripheral neuropathy is a frequent complication of long-standing diabetes mellitus that adversely affects the quality of life. Pregabalin (anticonvulsant) and duloxetine (antidepressant) are often prescribed for diabetic peripheral neuropathic pain. This study aimed to determine and compare the efficacy and safety of pregabalin and duloxetine in patients with diabetic peripheral neuropathic pain. Materials and methods This prospective observational study was conducted at District Headquarter (DHQ) Hospital, Daggar, Buner district, Pakistan, from February 15 to July 15, 2022, after approval from the Institutional Research and Ethical Review Board. Confirmation of diabetic peripheral neuropathy was based on the history of diabetes mellitus and vibration perception threshold (VPT) using a biothesiometer. The cut-off was set at 15 volts. VPT of more than 15 volts was considered confirmatory for peripheral neuropathy. Patients were divided equally into two groups. Baseline visual analog scale (VAS) score was recorded for all patients. Tablet pregabalin 300 mg daily was administered for four weeks to one group, while tablet duloxetine in 60 mg strength daily was administered to the other group. VAS score after four-week treatment was recorded and compared. Adverse events experienced by the patient were also noted. Results A total of 86 patients were enrolled. The patient ages ranged from 30 to 80 years. Baseline characteristics, including mean age, mean BMI, and mean disease duration of duloxetine versus pregabalin group, were 50.30 ± 8.55 versus 48.20 ± 8.99 years, 23.47 ± 1.23 versus 23.10 ± 1.59 kg/m2 and 21.64 ±7.41 versus 20.04±6.37 months respectively. Duloxetine effectively controlled peripheral neuropathic pain in 81.4% of patients compared to pregabalin in 74.4% of patients. Severe drug-related adverse reactions were observed in 4.6% of patients with duloxetine compared to 0% with pregabalin. Conclusion Duloxetine and pregabalin effectively reduce diabetes-related peripheral neuropathic pain. However, duloxetine has slightly better outcomes than pregabalin. The safety profile of pregabalin is better than duloxetine.

Circulating MicroRNAs as Biomarkers of Accelerated Sarcopenia in Chronic Heart Failure.

Background: Sarcopenia is a critical finding in patients with chronic heart failure (CHF). However, the search for a definitive biomarker to predict muscle and functional decline in CHF remains elusive. Objectives: We aimed to correlate the circulating levels of selected miRs with the indexes of sarcopenia during healthy aging and in patients with CHF. Methods: We analyzed the association of circulating microRNAs (miRs) levels including miR-21, miR-434-3p, miR424-5p, miR-133a, miR-455-3p and miR-181a with sarcopenia indexes in male, 61-73 years old healthy controls and patients with CHF (N = 89-92/group). Results: Patients with CHF had lower hand-grip strength (HGS), appendicular skeletal mass index (ASMI) and physical capacity than healthy controls. Circulating miR-21 levels were higher and miR-181a, miR-133a, miR-434-3p and miR-455-3p levels were lower in patients with CHF than healthy controls. Among the sarcopenia indexes, HGS showed the strongest correlation with miR-133a while ASMI showed the strongest correlations with miR-133a, miR-434-3p and miR-455-3p. Among the miRs, miR-434-3p showed the highest area under the curve in testing for sensitivity and specificity for CHF. These changes were associated with higher expressions of the markers of inflammation, oxidative stress and muscle damage in CHF patients. Conclusion: Taken together, our data show that circulating miRs can be useful markers of muscle health and physical capacity in the sarcopenic elderly with CHF.

Prediction of sarcopenia using a battery of circulating biomarkers.

Loss of muscle mass and strength with aging, termed sarcopenia is accelerated in several comorbidities including chronic heart failure (CHF) and chronic obstructive pulmonary diseases (COPD). However, the effective circulating biomarkers to accurately diagnose and assess sarcopenia are not known. We recruited male healthy controls and patients with CHF and COPD (n = 81-87/group), aged 55-74 years. Sarcopenia was clinically identified based on hand-grip strength, appendicular skeletal muscle index and physical capacity as recommended by the European working group for sarcopenia. The serum levels of amino-terminal pro-peptide of type-III procollagen, c-terminal agrin fragment-22, osteonectin, irisin, fatty acid-binding protein-3 and macrophage migration inhibitory factor were significantly different between healthy controls and patients with CHF and COPD. Risk scores for individual biomarkers were calculated by logistic regressions and combined into a cumulative risk score. The median cutoff value of 3.86 was used to divide subjects into high- and low-risk groups for sarcopenia with the area under the curve of 0.793 (95% CI = 0.738-0.845, p < 0.001). A significantly higher incidence of clinical sarcopenia was found in high-risk group. Taken together, the battery of biomarkers can be an effective tool in the early diagnosis and assessment of sarcopenia.

Efficacy and Safety of Sofosbuvir and Velpatasvir Combination for the Treatment of Chronic Hepatitis C in Patients With or Without Cirrhosis.

Background and aim For years, interferon-based treatment has been offered to patients with chronic hepatitis C virus (HCV) infection; however, the complexity of the treatment, efficacy, and adverse effects were the primary concerns. All these concerns were addressed with the introduction of directly acting antivirals (DAAs) to treat chronic HCV. Sofosbuvir and velpatasvir are second-generation DAAs used in combination for the treatment of chronic HCV infection. The aim of our study was to determine and compare the efficacy and safety profile of the sofosbuvir and velpatasvir combination in treating patients with chronic hepatitis C with or without cirrhosis. Materials and methods This descriptive study was conducted at the Department of Medicine, Khyber Teaching Hospital, Peshawar, from March 15th to September 15th, 2021 after approval from the Institution Research and Ethical Review Board (IREB). Diagnosis of HCV was based on the detection of hepatitis C ribonucleic acid (RNA) fragments by reverse transcription-polymerase chain reaction (RT-PCR). Liver status was assessed with liver function tests and imaging. Sofosbuvir (400 mg) and velpatasvir (100 mg) were administered once daily for 12 weeks, followed by polymerase chain reaction (PCR) for HCV RNA after 12 weeks of completion of treatment for determination of sustained virologic response at 12 weeks (SVR12). Patients with cirrhosis also received weight-based ribavirin. Adverse events experienced by the study participants during the course of treatment were recorded. Data were collected regarding patients' demographics, laboratory parameters, SVR12, and adverse events, and were then analyzed using SPSS, version 22 (IBM SPSS Statistics, Armonk, NY). Results A total of 58 patients with cirrhosis and 58 patients without cirrhosis with chronic HCV were enrolled. The rate of SVR12 in patients with cirrhosis was 89.7% (52 patients achieved SVR12), compared to 98.3% in patients without cirrhosis (57 patients achieved SVR12). Subgroup analysis of patients with cirrhosis revealed that patients who have failed to achieve SVR12 were mostly males, had prolonged disease duration, and low hemoglobin at baseline; however, the association of these factors with SVR12 was not significant. The incidence of adverse events among all study participants was 46.5%. Among the cirrhotic cohort, 37 (63.8%) patients experienced adverse events, while only 17 (29.3%) patients among the non-cirrhotic cohort had adverse events. A total of 24 patients with cirrhosis (41.37%) reported mild complaints. The most commonly reported adverse event was gastrointestinal (GI) upsets (46.2%), followed by fatigue (33.9%), while 19.9% developed miscellaneous adverse events such as headaches, rash, and insomnia. Conclusion The combination of sofosbuvir and velpatasvir is highly effective and safe in patients with HCV with or without cirrhosis. However, this combination's efficacy was slightly higher in non-cirrhotic patients (98.3%) than in cirrhotic patients (89.7%).

Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases.

Skeletal muscle dysfunction is a critical finding in many respiratory diseases. However, a definitive biomarker to assess muscle decline in respiratory diseases is not known. We analyzed the association of plasma levels of glycoprotein Dickkopf-3 (Dkk-3), c-terminal agrin fragment-22 (CAF22) and microRNAs miR-21, miR-134a, miR-133 and miR-206 with hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in male, 54-73-year-old patients with chronic obstructive pulmonary diseases (COPD), asthma or pulmonary TB (n = 83-101/group). Patients with respiratory diseases showed a reduction in HGS and gait speed, while a reduction in ASMI was only found in patients with pulmonary TB. Among the sarcopenia indexes, HGS showed the strongest correlation with plasma CAF22, miR-21 and miR-206 levels while ASMI showed the strongest correlation with Dkk-3 and miR-133 in respiratory diseases. We found a modest-to-significant increase in the plasma markers of inflammation, oxidative stress and muscle damage, which had varying degrees of correlations with Dkk-3, CAF22 and selected micro RNAs (miRs) in respiratory diseases. Taken together, our data show that plasma levels of Dkk-3, CAF22 and selected miRs can be useful tools to assess accelerated sarcopenia phenotype in the elderly with respiratory diseases.