Immunological signature in human cases of monkeypox infection in 2022 outbreak: an observational study.

BACKGROUND: An unprecedented global monkeypox outbreak started in May, 2022. No data are yet available about the dynamics of the immune response against monkeypox virus. The aim of this study was to describe kinetics of T-cell response, inflammatory profile, and pox-specific T-cell induction in patients with laboratory-confirmed monkeypox. METHODS: 17 patients with laboratory-confirmed monkeypox admitted at the Lazzaro Spallanzani National Institute for Infectious Diseases (Rome, Italy), from May 19, to July 7, 2022, were tested for differentiation and activation profile of CD4 and CD8 T (expression of CD38, PD-1, and CD57 assessed by flow cytometry), frequency of pox-specific T cells (by standard interferon-γ ELISpot), and release of interleukin (IL)-1ß, IL-6, IL-8, and tumour necrosis factor (TNF) in plasma (by ELISA). All patients were tested 10-12 days after symptoms onset. In a subgroup of nine patients with a laboratory-confirmed monkeypox, the kinetics of the immune response were analysed longitudinally according to timing from symptoms onset and compared with ten healthy donors (ie, health-care workers recruited from the same institution). FINDINGS: Among the 17 patients, ten were HIV negative and seven HIV positive, all with good viro-immunological status. On days 0-3 from symptom onset, patients with laboratory-confirmed monkeypox were characterised by a statistically significant reduction in CD4+ T cells (p=0·0011) and a concurrent increase of CD8+ T cells (p=0·0057) compared with healthy donors. A lower proportion of naive (CD45RA+CD27+) CD4+ T cells was observed in six (67%) of nine patients and a concomitant higher proportion of effector memory (CD45RA-CD27-) CD4+ T cells in all patients; this skewed immune profile tended to normalise over time. A similar differentiated profile was also observed in CD8+ T cells with a consistent expansion of terminally differentiated CD8+ T cells. Patients with monkeypox had a higher proportion of CD4+CD38+ and CD38+CD8+ T-cells than healthy donors, which normalised after 12-20 days from symptom onset. The expression of PD-1 and CD57 on CD4+ and CD8+ T-cells showed kinetics similar to that observed for CD38. Furthermore, the inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF) were higher in patients with monkeypox than in healthy donors and, although they decreased over time, they remained elevated after recovery. Almost all patients (15 [94%] of 16) developed a pox-specific Th1 response. No differences in immune cells profile were observed between patients with and without HIV, whereas paucysimptomatic patients (without systemic symptoms, with less than five skin lesions, and no other mucosal localisation of monkeypox) showed a less perturbed immune profile early after symptom onset. INTERPRETATION: Our data showed the immunological signature of monkeypox virus infection, characterised by an early expansion of activated effector CD4+ and CD8+ T cells that persisted over time. Almost all patients, even regardless of HIV infection, developed a poxvirus-specific Th1 cell response. These results might have implications on the expected immunogenicity of monkeypox vaccination, suggesting that it might not be necessary to vaccinate people who have already been infected. FUNDING: Italian Ministry of Health. TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Viral replication in the respiratory tract induces the death of infected cells and the release of pathogen- associated molecular patterns (PAMPs). PAMPs give rise to local inflammation, increasing the secretion of pro- inflammatory cytokines and chemokines, which attract immune cells from the blood into the infected lung. In most individuals, lung-recruited cells clear the infection, and the immune response retreats. However, in some cases, a dysfunctional immune response occurs, which triggers a cytokine storm in the lung, leading to acute respiratory distress syndrome (ARDS). Severe COVID-19 is characterized by an impaired innate and adaptive immune response and by a massive expansion of myeloid-derived suppressor cells (MDSCs). MDSCs function as protective regulators of the immune response, protecting the host from over-immunoreactivity and hyper-inflammation. However, under certain conditions, such as chronic inflammation and cancer, MDSCs could exert a detrimental role. Accordingly, the early expansion of MDSCs in COVID-19 is able to predict the fatal outcome of the infection. Here, we review recent data on MDSCs during COVID-19, discussing how they can influence the course of the disease and whether they could be considered as biomarker and possible targets for new therapeutic approaches.

Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection.

Massive platelet activation and thrombotic events characterize severe COVID-19, highlighting their critical role in SARS-CoV-2-induced immunopathology. Since there is a well-described expansion of myeloid-derived suppressor cells (MDSC) in severe COVID-19, we evaluated their possible role in platelet activation during SARS-CoV-2 infection. During COVID-19, a lower plasmatic L-arginine level was observed compared to healthy donors, which correlated with MDSC frequency. Additionally, activated GPIIb/IIIa complex (PAC-1) expression was higher on platelets from severe COVID-19 patients compared to healthy controls and inversely correlated with L-arginine plasmatic concentration. Notably, MDSC were able to induce PAC-1 expression in vitro by reducing L-arginine concentration, indicating a direct role of PMN-MDSC in platelet activation. Accordingly, we found a positive correlation between ex vivo platelet PAC-1 expression and PMN-MDSC frequency. Overall, our data demonstrate the involvement of PMN-MDSC in triggering platelet activation during COVID-19, highlighting a novel role of MDSC in driving COVID-19 pathogenesis.

Outcomes of sutureless total thyroidectomy in elderly.

INTRODUCTION: Thyroid disease is common in elderly population. The incidence of hypothyroidism and multinodular goiter increases with age. Surgery in elderly patients has been considered to be more hazardous than in a youthful population. Besides the traditional surgical hemostatic techniques, different hemostatic approaches, which further minimize the risk of bleeding and complications during thyroidectomy, have become available. Aim of this study was to review and compare the outcomes of total thyroidectomy (TT) in elderly performed with different energy system. METHODS: A total of 255 patients were eligible for the study and enrolled. One hundred and five patients with age >70 years (median age 76, range 70-90) constituted the elderly group (EG), whereas the young group (YG) was composed by 150 patients (median age 36, range 18-69). Each group was further divided into three subgroups, on the basis of the device used (none, Ligasure Precise/Small Jaw or Harmonic Focus) for performing TT as follows: conventional thyroidectomy in EG (CTE) and YG (CTY), Ligasure thyroidectomy (LTE and LTY) and Harmonic thyroidectomy (THE and HTY). Intra-operative and post-operative data, as well as complications rate, were collected. RESULTS: There was no significant difference between the elderly and the young patients treated with total thyroidectomy. Using of Harmonic Focus or Ligasure Precise/Small Jaw allowed a reduction of the duration of surgery (p < 0.05) than conventional approach; complication rate for hemorrhage, hypocalcemia and vocal cord paralysis was similar in all sub-groups. CONCLUSIONS: Total thyroidectomy in elderly patients is as safe as in the younger population. Moreover, using the Harmonic Focus and the Ligasure Precise/Small Jaw is a safe, effective, and time-saving alternative to the traditional suture ligation technique for thyroid surgery.

Esophagogastric junction morphology assessment by high resolution manometry in obese patients candidate to bariatric surgery.

INTRODUCTION: Obesity is a strong independent risk factor of gastroesophageal reflux disease (GERD) symptoms and hiatal hernia development. Pure restrictive bariatric surgery should not be indicated in case of hiatal hernia and GERD. However it is unclear what is the real incidence of disruption of esophagogastric junction (EGJ) in patients candidate to bariatric surgery. Actually, high resolution manometry (HRM) can provide accurate information about EGJ morphology. Aim of this study was to describe the EGJ morphology determined by HRM in obese patients candidate to bariatric surgery and to verify if different EGJ morphologies are associated to GERD-related symptoms presence. METHODS: All patients underwent a standardized questionnaire for symptom presence and severity, upper endoscopy, high resolution manometry (HRM). EGJ was classified as: Type I, no separation between the lower esophageal sphincter (LES) and crural diaphragm (CD); Type II, minimal separation (>1 and < 2 cm); Type III, >2 cm separation. RESULTS: One hundred thirty-eight obese (BMI>35) subjects were studied. Ninety-eight obese patients referred at least one GERD-related symptom, whereas 40 subjects were symptom-free. According to HRM features, EGJ Type I morphology was documented in 51 (36.9%) patients, Type II in 48 (34.8%) and Type III in 39 (28.3%). EGJ Type III subjects were more frequently associated to Symptoms than EGJ Type I (38/39, 97.4%, vs. 21/59, 41.1% p < 0.001). CONCLUSIONS: Obese subjects candidate to bariatric surgery have a high risk of disruption of EGJ morphology. In particular, obese patients with hiatal hernia often refer pre-operative presence of GERD symptoms. Testing obese patients with HRM before undergoing bariatric surgery, especially for restrictive procedures, can be useful for assessing presence of hiatal hernia.

Effectiveness of an advanced hemostatic pad combined with harmonic scalpel in thyroid surgery. A prospective study.

INTRODUCTION: Hemostasis during thyroidectomy is essential; however the most efficient and cost-effective way to achieve this is unclear. The aim of this study was to evaluate the outcome of total thyroidectomy (TT) performed with the combination of harmonic scalpel (HS) and an advanced hemostatic pad (Hemopatch). METHODS: Patient undergone TT were divided into two groups: HS + hemopatch and HS + traditional hemostasis groups. The primary endpoint was 24-h drain output and blood-loss requiring reintervention. Secondary endpoints included surgery duration, postsurgical complications and hypocalcemia rates. RESULTS: Between September 2014 and March 2015, 60 patients were enrolled (30 to Hs + Hemopatch, 30 to Hs and standard hemostasis); 71.4% female; mean age 48.5 years. The 24-h drain output was lower in the HS + hemopatch group compared with standard TT. HS and hemopatch also had a shorter mean surgery time (p < 0.0001) vs standard TT. CONCLUSION: combination of hemopatch plus HS is effective and safe for TT with a complementary hemostatic approach.

Gastroesophageal reflux disease and obesity: do we need to perform reflux testing in all candidates to bariatric surgery?

INTRODUCTION: Obesity is a strong independent risk factor of gastroesophageal reflux disease (GERD) symptoms and esophageal erosions. However the relationship between obesity and GERD is still a subject of debate. In fact, if in most cases bariatric surgery can diminish reflux by losing a large amount of fat, on the other hand some restrictive procedure can worsen or cause the presence of GERD. Thus, it is unclear if patients candidate to bariatric surgery have to perform pre-operative reflux testing or not. AIM: of the study was to verify the presence of GERD patterns in patients candidate to surgery and the need of pre-operative reflux testing. METHODS: All patients underwent to a standardized questionnaire for symptoms severity (GERQ), upper endoscopy, high resolution manometry (HRiM) and impedance pH-monitoring (MII-pH). Patients were stratified into: group 1 (negative for both GERQ and endoscopy), group 2 (positive for GERQ and negative for endoscopy), group 3 (positive for both GERQ and endoscopy). A healthy-volunteers group (HV) was assessed. RESULTS: One hundred thirty-nine subjects (obese, 124; HV normal weight, 15) were studied. Group 1 showed comparable mean LES pressure, peristaltic function, bolus transport and presence of hiatal hernia than HV. Group 2 showed a reduction of these parameters, while group 3 showed a statistical significant reduction in LES pressure, peristaltic function, bolus transport and increase in presence of hiatal hernia. At MII-pH, Group 1 showed a not significant increase in reflux patterns; group 2 and 3 showed a significant increase in esophageal acid exposure and in number of refluxes (both acid and weakly acid), with group 3 showing the higher grade of reflux pattern. CONCLUSIONS: Obese subjects with pre-operative presence of GERD symptoms and endoscopical signs could be tested with HRM and MII-pH before undergoing bariatric surgery, especially for restrictive procedures. On the other hand, obese patients without any sign of GERD could not be tested for reflux, showing similar patterns to HV.

Sutureless thyroidectomy.

OBJECTIVE: The ultrasonic scalpel is a surgical shear that uses high-frequency mechanical energy to enable simultaneous vessel sealing and tissue coagulation at the same time. We conducted a prospective study to compare the outcome of total thyroidectomy using the ultrasonic scalpel versus the device Ligasure in terms of safety, operative time, overall drainage volume, complications, hospital stay. METHODS: Between January 2008 and December 2013,400 patients (260 women, 140 men; mean age 46 years) undergoing thyroidectomy were randomized into two groups: group A, where Ultracision were used, and group B, where the Ligasure device was used. RESULTS: There was no significant differences between the two groups in terms of age, gender, indication for thyroidectomy, thyroid gland weight and diameter, histopathologic diagnosis, preoperative and postoperative serum calcium levels, postoperative complications and reoperative thyroid surgery, time of operation and amount of drainage. CONCLUSIONS: The ultrasonic scalpel and the Ligasure ares safe, effective, useful, and time-saving alternative to the traditional suture ligation technique for thyroid surgery. They simplified total thyroidectomy, eliminating the need for clamp-and-tie maneuvers while achieving efficient hemostasis.

Axillary lymphadenectomy for breast cancer and fibrin glue.

BACKGROUND: Axillary lymphadenectomy or sentinel biopsy is integral part of breast cancer treatment, yet seroma formation occurs in 15-85% of cases. Among methods employed to reduce seroma magnitude and duration, fibrin glue has been proposed in numerous studies with controversial results. METHODS: Eighty patients underwent quadrantectomy or mastectomy with level I/II axillary lymphadenectomy; a suction drain was fitted in all patients. Fibrin glue spray were applied to the axillary fossa in 40 patients; the other 40 patients were treated conventionally. RESULTS: Suction drainage was removed between post-operative Days 3 and 4. Seroma magnitude and duration were significantly reduced (p=0.004 and 0.02, respectively), and there were fewer evacuative punctures, in patients receiving fibrin glue compared with the conventional treatment group. CONCLUSIONS: Use of fibrin glue does not always prevent seroma formation, but does reduce seroma magnitude, duration and necessary evacuative punctures.

Axillary lymphadenectomy for breast cancer in elderly patients and fibrin glue.

BACKGROUND: Axillary lymphadenectomy or sentinel biopsy is integral part of breast cancer treatment, yet seroma formation occurs in 15-85% of cases. Among methods employed to reduce seroma magnitude and duration, fibrin glue has been proposed in numerous studies with controversial results. METHODS: Thirty patients over 60 years underwent quadrantectomy or mastectomy with level I/II axillary lymphadenectomy; a suction drain was fitted in all patients. Fibrin glue spray were applied to the axillary fossa in 15 patients; the other 15 patients were treated with harmonic scalpel. RESULTS: Suction drainage was removed between post-operative Days 3 and 4. Seroma magnitude and duration were not significant in patients receiving fibrin glue compared with the harmonic scalpel group. CONCLUSIONS: Use of fibrin glue does not always prevent seroma formation, but can reduce seroma magnitude, duration and necessary evacuative punctures.

Long term quality of life after laparoscopic antireflux surgery for the elderly.

BACKGROUND: Studies have previously shown laparoscopic antireflux surgery is a safe and effective treatment for GERD even in elderly patients. The aim of the current study was to evaluate patients receiving laparoscopic antireflux surgery before and after 65 years of age and to assess their surgical outcomes and improvements in long term quality of life. METHODS: Patients were given a standardized symptoms questionnaire and the Short-Form 36 Health Survey for quality-of-life evaluation before and after laparoscopic total fundoplication. RESULTS: Forty-nine patients older than 65 years of age were defined as the elderly group (EG) whereas the remaining 262 younger than 65 years of age were defined as the young group (YG). CONCLUSIONS: In conclusion, laparoscopic total fundoplication is a safe and effective surgical treatment for gastroesophageal reflux disease generally warranting low morbidity and mortality rates and a significant improvement of symptoms comparable. An improved long-term quality of life is warranted even in the elderly.

Minimally invasive thyroidectomy (MIT): indications and results.

AIM: To establish if the indication for different approaches for thyroidectomy and the incision length provided by means of pre-operative assessment of gland volume and size of nodules resulted in safe and effective outcomes and in any notable aesthetic or quality-of-life impact on patients. MATERIALS AND METHODS: Ninehundred eightytwo consecutive patients, undergoing total thyroidectomy, were enrolled. The thyroid volume and maximal nodule diameter were measured by means of ultrasounds. Based on ultrasounds findings, patients were divided into three groups: minimally invasive video assisted thyroidectomy (MIVAT), minimally invasive thyroidectomy (MIT) and conventional thyroidectomy (CT) groups. The data concerning the following parameters were collected: operative time, postoperative complications, postoperative pain and cosmetic results. RESULTS: The MIVAT group included 179 patients, MIT group included 592 patients and CT group included 211 patients. Incidence of complications did not differ significantly in each group. In MIVAT and MIT group, the perception of postoperative pain was less intense than CT group. The patients in the MIVAT (7±1.5) and MIT (8±2) groups were more satisfied with the cosmetic results than those in CT group (5±1.3) (p= <0.05). CONCLUSIONS: The MIT is a technique totally reproducible, and easily convertible to perform surgical procedures in respect of the patient, without additional complications, increased costs, and with better aesthetic results.

Hyaluronic acid and adhesions on polypropylene endoperitoneal mesh: an experimental study.

INTRODUCTION: The aim of this study was to verify the effectiveness of hyaluronic acid in preventing adhesion formation after endoperitoneal surgery in which prosthetic polypropylene mesh is placed directly on the viscera. METHODS: Forty albino rats were included in this study and the animals were randomized to the following 4 groups each with 10 rats: polypropylene prosthesis (PP), PP+hyaluronic acid (HA), Hertra prosthesis (HP), HP+HA. A large defect was created in the anterior abdominal wall of each rat and repaired in different ways. In the first group a polypropylene mesh was placed intraperitoneally, while, in the second group the peritoneal surface of the mesh was impregnated with HA. In the third group a Hertra 0 polypropylene rigid mesh was placed intraperitoneally and, in the fourth group, the peritoneal surface of the Hertra 0 mesh was impregnated with HA. Clinical controls on the animals were carried out at 1 month. Each group was divided into two subgroups in which the controls and the prosthetic explantation were randomly carried out at 3 and 6 months. Explanted prostheses were subjected to histological and immunohistochemical analysis, and examined for shrinkage. An assessment of adhesion formation was performed, evaluating the quantity and tenacity of the adhesions. RESULTS: We demonstrated higher levels of adhesions in rats with PP than in those with HP and lower levels in rats with a protective layer of hyaluronic acid. The amount of fibronectin in the periprosthetic fibrotic tissue and the histological score confirmed the previous data. CONCLUSIONS: Hertra 0 mesh with HA provided the best results in terms of physical stability and resistance to adhesion formation.

Ultrasound scalpel in thyroidectomy. Prospective randomized study.

OBJECTIVE: The ultrasonic scalpel is a surgical shear that uses high-frequency mechanical energy to enable simultaneous vessel sealing and tissue coagulation at the same time. We conducted a prospective randomized study to compare the outcome of total thyroidectomy using the ultrasonic scalpel versus standard clamp and tie (CT) procedure in terms of safety, operative time, overall drainage volume, complications, hospital stay. METHODS: Between January 2008 and December 2010, 200 patients (130 women, 70 men; mean age 46 years) undergoing thyroidectomy were randomized into two groups: group A, where CT technique were used, and group B, where the ultrasonic device was used. RESULTS: There was no significant differences between the two groups in terms of age, gender, indication for thyroidectomy, thyroid gland weight and diameter, histopathologic diagnosis, preoperative and postoperative serum calcium levels, postoperative complications and reoperative thyroid surgery. In group B there is a statistically significant reduction of the operative times (63 ± 9' vs 85 ± 15', P<0.001) and overall drainage volume (50 ± 20cc vs 70 ± 25cc, P<0.001) . CONCLUSIONS: The ultrasonic scalpel is safe, effective, useful, and time-saving alternative to the traditional suture ligation technique for thyroid surgery. They simplified total thyroidectomy, eliminating the need for clamp-and-tie maneuvers while achieving efficient hemostasis. Our study shows that the use of ultrasound in thyroid surgery reduces significantly surgical time and overall drainage volume. Furthermore, we also verified a decrease in hospitalization time, postoperative pain and blood loss, without increasing complication rates, for patients who underwent total thyroidectomy with the ultrasonically activated shear.

Effectiveness of fibrin glue in conjunction with collagen patches to reduce seroma formation after axillary lymphadenectomy for breast cancer.

BACKGROUND: Axillary lymphadenectomy remains an integral part of breast cancer treatment, yet seroma formation occurs in 15% to 85% of cases. Among methods employed to reduce seroma magnitude and duration, fibrin glue has been proposed in numerous studies, with controversial results. METHODS: Fifty patients underwent quadrantectomy or mastectomy with level I/II axillary lymphadenectomy; a suction drain was fitted in all patients. Fibrin glue spray and a collagen patch were applied to the axillary fossa in 25 patients; the other 25 patients were treated conventionally. RESULTS: Suction drainage was removed between postoperative days 3 and 4. Seroma magnitude and duration were significantly reduced (P = .004 and .02, respectively) and there were fewer evacuative punctures in patients receiving fibrin glue and collagen patches compared with the conventional treatment group. CONCLUSIONS: Use of fibrin glue with collagen patches does not always prevent seroma formation, but it does reduce seroma magnitude and duration, as well as necessary evacuative punctures.

Umbilical endometriosis associated with umbilical hernia. Management of a rare occurrence.

We report a rare case of primitive umbilical endometriosis associated with umbilical hernia, which required wide umbilical resection and immediate reconstruction performed according to a recently described technique. A wide resection of the peritoneal sac was performed because of the possible presence of endometrial tissue inside. The hernia was repaired according to Mayo's technique. Umbilical reconstruction was performed using two semicircular skin flaps shaped into in an ellipse preoperatively drawn on the skin with a vertical orientation. The surgical approach described in this report allowed easy hernia repair and umbilical reconstruction. No prosthesis was used because of the small size of the hernia and lack of literature data on prosthesis use in endometriosis. The aesthetic result was considered satisfactory 6 months after the operation because of absence of hypertrophic scars and in view of the anatomical aspect of the new umbilicus. No recurrence was observed within this time frame.