Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.

INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis. METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis. RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04). CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.

Effects of Oral Zafirlukast, Sildenafil, or Pirfenidone on the Formation of Postsurgical Intra-Abdominal Adhesions in an Experimental Rat Model.

INTRODUCTION: Intra-abdominal adhesions' main etiology is surgical procedures that commonly require reintervention. Oral treatments with sildenafil, zafirlukast, and pirfenidone have yielded decreased severity of fibrotic phenomena secondary to the introduction of foreign material. This study aimed to evaluate the efficacy of oral zafirlukast, sildenafil, or pirfenidone treatment on reducing or preventing intra-abdominal adhesions in an experimental rat model. METHODS: Four groups, each of 10 male Wistar rats weighing 250-300 g, were used. A midline laparotomy was used to excise an area of 1.5 × 1.5 cm and reconstructed with polypropylene mesh fixed to the abdominal wall. After 12 h, oral doses of zafirlukast (1.25 mg/kg, group B), sildenafil (15 mg/kg, group C), or pirfenidone (500 mg/kg, group D) were given every day for 8 days. The control group, A, received no treatment. At day 9, animals were reoperated. The implant was resected after ethically approved euthanasia, and specimens were fixed in 10% formaldehyde for histopathology. RESULTS: Control group A yielded adhesions with greater fibrovascular density and neighboring organ involvement than the other groups (p = 0.001), as well as intense inflammatory infiltrates and numerous granulomas (p = 0.04). Adhesions in group C had less fibrovascular density (p = 0.03) with decreased serosal injuries (p = 0.001) and less organ involvement. Group D had reduced adhesions without organ involvement (p < 0.01) and less inflammatory infiltrates, collagen fibers, and foreign body granulomas than group B or C (p < 0.01). CONCLUSIONS: Oral administration of these agents did not prevent adhesions but ameliorated them. Oral pirfenidone offered the best performance and could be recommended for human use.

Substance Use and Psychological Distress in Mexican Adults during COVID-19 Pandemic: A Cross-Sectional Study.

OBJECTIVES: This observational cross-sectional study examined changes in substance use during the coronavirus disease 2019 (COVID-19) pandemic in the Mexican population and evaluated whether depression or anxiety was associated with these new consumption patterns. METHODS: An online survey was distributed to the general population. Participants were questioned about their demographics, situation during the COVID-19 pandemic, and substance consumption patterns. The Patient Health Questionnaire-9 for depression and the Coronavirus Anxiety Scale were used. RESULTS: A total of 866 individuals completed the survey. The mean scores for the Patient Health Questionnaire-9 and Coronavirus Anxiety Scale were 8.89 ± 6.20 and 3.48 ± 3.22, respectively. The preferred substances were alcohol (19%), tobacco (16.5%), and marijuana (5.6%). Consumption of alcohol (p = 0.042) significantly increased during the pandemic and it was higher in women than in men (p = 0.040). CONCLUSIONS: Substance use patterns were affected by the pandemic, with an increase in the number of users and consumption rate, as well as the reported psychiatric symptoms.

The Benefit of Perineural Injection Treatment with Dextrose for Treatment of Chondromalacia Patella in Participants Receiving Home Physical Therapy: A Pilot Randomized Clinical Trial.

Introduction: Chondromalacia patella is the degeneration of articular cartilage on the posterior facet of the patella and may indicate the onset of osteoarthritis. Conservative management is the main treatment option, and surgical intervention is considered the last option in a small percentage of patients. Perineural Injection Treatment (PIT) is a recently developed treatment option that is directed adjacent to the peripheral nerves that are the source of pathology causing neurogenic inflammation and pain. Objective: The objective of this study was to evaluate the efficacy of PIT combined with a home physical therapy program in patients with a diagnosis of chondromalacia patella compared with a control group receiving physical therapy only. Methods: Two patient groups were involved in this randomized clinical trial. The first received PIT combined with physical therapy (PIT + PT group) and the second was managed with physical therapy alone (PT group). Both groups were indicated to follow a 6-week home therapy plan afterward. The Western Ontario and McMaster Osteoarthritis Index was used to assess the patients at baseline and 6 months after therapy interventions. Results: Fifty patients (38 women and 12 men, median age 54.7 ± 14.8 years) were included; sex distribution and age did not differ between groups. Both groups had chondromalacia grade II or III, but the degree of gonarthrosis did not differ significantly between groups. The PIT + PT group outperformed PT group for pain (7.3 ± 3.5 vs. 3.2 ± 2.9 points; p < 0.010), stiffness (3 ± 1.69 vs. 1.6 ± 1.5 points; p < 0.010), and functional capacity (23.2 ± 10.7 vs. 11.1 ± 8.9 points; p < 0.010). Conclusions: Compared with physical therapy alone, PIT plus physical therapy reduced pain and stiffness and restored functional capacity. ClinicalTrials.gov Register Number #NCT03515720.

Gender Differences in Postoperative Pain, Nausea and Vomiting After Elective Laparoscopic Cholecystectomy.

BACKGROUND: Although reports suggest that pain and postoperative nausea and vomiting (PONV) may be more frequent in women, the evidence is inconsistent. The objective of this study was to investigate whether women are more sensitive to pain and PONV after laparoscopic cholecystectomy (LC). METHODS: A total of 370 women and 275 men were included in a retrospective cohort study. All underwent LC under standardized general anesthesia. The variables analyzed included clinical and anthropometric parameters. End points were the incidence of nausea, vomiting, pain, and the requirement for additional pain relievers and antiemetics to control these. RESULTS: The women were younger and had lower body weight than the men (p < 0.001). Body mass index was within the normal range for 50% of women and 30% of men (p < 0.001). Pain was more common in women at 1, 6, 12 and 24 h after surgery (p < 0.02). Narcotics in addition to the doses used to lessen pain intensity (p = 0.01) were required in 60 women and 19 men (p < 0.001). PONV was more frequent in women at 1 and 6 h after surgery (p < 0.01). Rescue antiemetics were required in 35 women and 11 men (p = 0.008). Hospital stay was shorter for men (p < 0.001). Four patients in each group developed postoperative complications (p = 0.14). There was no mortality. CONCLUSIONS: Early postoperative pain, nausea and vomiting after LC were more common in women, who more frequently required analgesic and antiemetic rescue medication.