Effective Treatment of Solitary Rectal Ulcer Syndrome by Using Photobiomodulation Therapy: A Case Report.

Objective: To investigate the efficacy of Photobiomodulation therapy (PBMT) for the treatment of solitary rectal ulcer syndrome (SRUS). Background: SRUS is a benign disease, diagnosed by symptoms, clinical, and histological findings. PBMT has been reported for the treatment of various inflammation-based diseases including aphthous ulcer, but still no such study on the treatment of SRUS is published. Materials and methods: A 29-year Asian women, diagnosed for SRUS of 0.57 cm diameter, was treated by a laser at 635 nm through seven sessions. Laser fluence of 85 J/cm2 was delivered to ulcer lesion during each session for 10 min. Clinical results were valued by physician with sigmoid probe throughout PBMT sessions and no medicines were prescribed to the patient. Results: After seven sessions, the lesion was completely healed with 100% clinical response. In follow-up, patient did not respond to any additional/recurring abnormality, and no side effects were observed. Conclusions: In conclusion, PBMT by using laser at 635 nm is an effective treatment for SRUS without any side effects and patient remained comfortable throughout treatment sessions. Patient registration No. H-744/23.

Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer.

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance.

Preventive Measures and Active Response against COVID-19 Taken by All Four Provinces, Two Independent Territories, and the Federal State of Islamic Republic of Pakistan, Islamabad.

The novel coronavirus disease outbreak started in December, 2019 in Wuhan, China. On March 11, 2020, WHO declared COVID-19 outbreak as a pandemic due to uncontrolled situation. Pakistani government management against COVID-19 was excellent having 204.65 million population, all four provinces, two independent territories, and federal state took different initiative in pandamic situation c. that's why the situation was under control in Pakistan due to state respond urgently to halt the spread of disease. With rapid response and full support of the government of Pakistan, the situation was under control in all aspects of life, June 17, 2019, each district of Pakistan recorded at least one confirmed case of COVID-19 due to remarkable effort against pandemic. The state of Pakistan declare urgency and fastest action to control the situation, economic package, ventilator manufacturing, and diagnostic kits were manufactured locally. The DRAP Pakistan permitted to use different drugs against COVID-19 and purchased vaccines from China. Due to the planning and management of the Pakistani Government, the situation was under control as compared with neighborhood countries (China and India), in both countries COVID-19 waves was lethal.

Efficacy and Safety of Generic Sofosbuvir Plus Daclatasvir and Sofosbuvir/Velpatasvir in HCV Genotype 3-Infected Patients: Real-World Outcomes From Pakistan.

BACKGROUND: Direct-acting antivirals (DAAs) therapeutic regimens are highly effective against chronic hepatitis C virus (HCV) infection. However, HCV patients with genotype 3 (GT3) respond in a suboptimal way. This study aims to identify which of the DAAs-based therapeutic regimens are the best option for GT3. METHODS: Multiple governments and private tertiary care hospitals were involved in this real-life study of HCV-GT3 patients treated with DAAs. The efficacy and safety of generic sofosbuvir+daclatasvir±ribavirin (SOF+DCV±RBV) and sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) were assessed under the National Hepatitis C Program of Pakistan. RESULTS: Out of 1,388 participants, 70% of patients received SOF+DCV in government tertiary care hospitals and 30% received SOF/VEL in private tertiary care hospitals. The overall sustained virological responses (SVR) was 95.5%. The SVR rates at 12 weeks were comparable between SOF+DCV (94.4%) and SOF/VEL (94.7%) in chronic HCV patients. However, The SVR rates at 24 weeks were high in cirrhotic patients treated with SOF/VEL+RBV (88%) then SOF+DCV+RBV (83%). Non-responders were high in SOF-DCV than SOF-VEL (4.1 vs 3.8%, P = 0.05) regimen. In multivariate models, the significant predictors of non-SVR were age >60 years (odds ratio [OR] 4.46; 95% CI, 2.35-8.46, P = <0.001) and cirrhosis (OR 53.91; 95% CI, 26.49-109.6, P = <0.001). Skin rash (51 vs 44%) and oral ulcers (45 vs 40%) were high in patients receiving SOF-DCV then SOF-VEL. CONCLUSIONS: Overall, the generic SOF+DCV ±RBV and SOF/VEL ± RBV achieved equally high SVR12 rates. However, SOF/VEL+RBV achieved a high SVR rate in cirrhotic patients then SOF+DCV+RBV. Old age and cirrhosis were significant predictors of reduced odds of SVR regardless of the regimen. Furthermore, the regimens were well tolerated in chronic HCV patients.

New Direct Acting Antiviral Agents for the Treatment of Hepatitis C: 2016 and Beyond.

Hepatitis C is one of the commonest public health problems with 130 million people infected worldwide and the burden is increasing. Previously, Interferon along with Ribavirin was the mainstay of treatment but it was associated with toxic side effects. An all-oral regimen with higher rates of sustained viral response (SVR), minimal side effects and no restriction for liver fibrosis staging, was long awaited. Several all-oral interferon-free direct acting antiviral agents (DAAs) have now been approved by FDAfor different genotypes of HCV. These include Sofosbuvir, Ledipasvir, Daclatasvir, Simeprevir, Dasabuvir, Ombitasvir, Paritaprevir and Ritonavir. These agents are also available in different combinations commercially under various trade names. Anumber of studies have proved their efficacy and the AASLD and EASLguidelines recommend several options for each genotype in different categories including treatment naïve, relapsers, failure, compensated and decompensated cirrhosis. The purpose of this article is to review the persistently changing treatment regimens for hepatitis C and to simplify the dynamicity of the subject and selection of appropriate regimen for these patients.

Diagnosis, Management And Prevention Of Hepatitis C In Pakistan 2017.

AIMS AND OBJECTIVES: Since the advent of direct acting antiviral agents, there is a revolutionary change in the management of HCV infection. Newer drugs with different mechanism of action are being introduced and are expected to be available in coming few months in Pakistan as well. The main purpose of the guideline is to review and induct the latest research in field of HCV infection in Pakistani perspective so that our healthcare professionals can apply the new recommendations in timely and judicial manner. Target groups of guidelines are general physicians treating hepatitis C, hepatologists and gastroenterologists. Other beneficiaries of these guidelines are public health institutions of Pakistan, which provide free treatment to deserving patients under National Hepatitis Prevention and Control Program and Pakistan Bait-ul- Mal Program. METHODOLOGY: These guidelines are based on the review of National consensus practice guidelines: Diagnosis, Management and Prevention of Hepatitis C Pakistan 2009. Published data in National and International Journals searched with the help of Google search and pub med, and 2015-16 guidelines of HCV by AASLD, EASL, APASL and WHO. Local studies are preferably added with references to enhance the Pakistani perspective. Evidence was also taken from published studies. Recommendations have been based upon evidence from national publications on the subject and scientific presentations at national liver meeting as well from experts' personal experience and opinion.

Role Of Generics In Treatment Of Hepatitis C Infection.

With the discovery of newer and newer DAAs, the cure of Hepatitis C seems to be a reality. But their high price and availability is a big hindrance. Sofosbuvir launched by Gilead costs about $ 84000 per 12-week course. Since its launch there is a huge debate regarding the complex pricing mechanism of DAAs. The pricing involves negotiation of patent holder with health insurance companies through their Pharmacy Benefit Managers (PBMs). Several rebates are also involved in this pricing mechanism amongst which only few are declared ones. Different countries are adapting different strategies to overcome this pricing issue. The branded companies have also issued licenses to companies to form generic version of the drugs and to market them to selected middle and low income countries. Few countries that are not in the list have rejected the patent and started producing their own generics. It is due to these generics that the price of DAAs had undergone a significant reduction but their manufacturing and efficacy needs regular scrutiny.

Issues Pertaining To Daas.

With the discovery of DAAs, the treatment of hepatitis C has improved a lot. But in this new era of DAAs several issues are also emerging. In this brief communication, we have tried to address the salient issues regarding DAAs.

Sofosbuvir For The Treatment Of Hepatitis C Genotype 3 Infected Patients In Pakistan.

BACKGROUND: This study was conducted to determine the viral responses of patients with chronic infection of Hepatitis C virus treated with sofubuvir. METHODS: This Quasi experimental study was conducted at Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi from September 2014 to September 2016. 502 patients with HCV genotype 3 including treatment naive, non-responders or relapsers to previous interferon based therapy along with patients having decompensated cirrhosis (child class B or C) were included in the study. All patients were treated with Sofosbuvir 400 mg once daily along with Ribavirin for 6 months. Follow-up qualitative PCR (polymerase Chain Reaction) were performed at 4 weeks interval to assess RVR (Rapid virological Response), end of treatment to determine ETR (End of treatment response) and 3 months post treatment to determine SVR12 (Sustained viral response at 12 week). RESULTS: 91% of the patients had become PCR negative at completion of four weeks of treatment with Sofosbuvir, whereas at completion of treatment 96.5% had attained a negative PCR. Sustained virological response at 12 weeks post therapy (SVR12) was attained in 85.5% of patients. No statistically significant associations were found with attainment status of RVR, ETR and SVR based on previous treatment status or presence of Decompensated liver disease. However, attainment of SVR was slightly more in females (p value=0.03). The serological profiles of patients whether they attained PCR at week 4, 24 of treatment or 12 weeks' post treatment did not exhibit any statistically significant difference. CONCLUSION: Sofosbuvir is effective in eradicating hepatitis C virus irrespective of previous treatment or liver fibrosis status in genotype 3 HCV Pakistani patients.