REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Hoigné's syndrome, an uncommon mimicker of anaphylaxis: Systematic literature review.

The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.

Reversed distal laterodigital adipofascial flap for nail-bed reconstruction.

BACKGROUND: Lesions of the distal phalanges of the fingers frequently involve the nail bed. There are few therapeutic options for nail-bed reconstruction and they often lead to painful scars and onychodystrophy. We present our experience with the distal adipofascial laterodigital reverse flap. METHODS: Fifteen patients (average age 46.33 years, range 28-73) with tumors or traumatic injuries (crush injuries, nail avulsion, and partial fingertip amputations) of the nail bed, underwent digital reconstruction through the distal adipofascial laterodigital reverse flap from June 2018 to August 2019. The size of the fingertip defect covered with the flap was ranged between 1.1 × 1.1 and 1.6 × 1.2 cm (average size 1.4 × 1.2 cm). The flap was harvested enrolling subcutaneous tissue from the lateral aspect of the middle and distal phalanx from the less damaged side. RESULTS: The average size of the harvested flaps was 1.3 × 1.2 cm (range 1.1 × 1.0 to 1.4 × 1.1 cm). All adipofascial flaps survived entirely and the nail bed healed in all patients, with an average healing time of 21 days and a subsequent regrowth of the nail. The follow up ranged from 6 to 12 months, with a mean of 7 months. CONCLUSIONS: The distal reverse adipofascial flap provides a very versatile and reliable coverage of the distal finger and its nail bed. It is a rapid and reproducible surgical procedure with poor morbidity for the donor site. LEVEL OF EVIDENCE: IV.

Nicolau syndrome caused by Glatiramer.

Injection-site reactions to glatiramer are common and include erythema, pruritus, pain, or induration. Additionally, the present systematic review of the literature documents 20 cases of Nicolau syndrome following glatiramer, a rare but potentially severe skin reaction. Abdomen and thighs are the most frequently affected areas (80% of reported cases), and permanent skin damage has been observed in 30% of cases. Recurrences are rare (<10%).

Clinical Predictors of Response to Anti-PD-1 First-Line Treatment in a Single-Centre Patient Cohort: A Real-World Study.

AIMS: Cutaneous melanoma is one of the most immunogenic tumours. Immunotherapy with checkpoint inhibitors, such as anti-PD-1 antibodies, has significantly improved the prognosis in metastatic melanoma. However, only half of the patients respond to this therapy and have a favourable outcome. Identifying factors associated with treatment failure and early identification of responders are both important to select the best treatment approach for each patient. The aim of our study was to investigate clinical biomarkers of response to treatment with anti-PD-1 antibodies. MATERIALS AND METHODS: We selected all patients with stage IV melanoma (n = 147), subjected to first-line treatment with anti-PD-1 in the last 10 years. We investigated the associations between patients' different clinical features and progression-free survival, using the Cox proportional hazards models. RESULTS: In the multivariate analysis, an increased risk of disease progression was observed among patients with stage M1d metastases (hazard ratio 3.30; 95% confidence interval 1.58-6.91), compared with patients with stage M1a-M1b. Moreover, the risk of progression was greater in patients with the Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1 (hazard ratio 2.04; 95% confidence interval 1.02-4.06) and in patients with ECOG PS ≥ 2 (hazard ratio 2.19; 95% confidence interval 1.05-4.55) compared with ECOG PS 0. High levels of lactate dehydrogenase (hazard ratio 2.06; 95% confidence interval 1.18-3.59) and the presence of respiratory diseases (hazard ratio 4.14; 95% confidence interval 1.42-12.0) at the beginning of anti-PD-1 treatment were also associated with an increased risk of disease progression. In a subgroup analysis, neutrophil count and neutrophil/lymphocyte ratio before anti-PD-1 treatment were higher in patients who underwent disease progression. CONCLUSION: In our study population, independent predictors of disease progression among patients treated with first-line anti-PD-1 were as follows: ECOG PS, staging, lactate dehydrogenase and the presence of respiratory diseases.

Management of surgical working in an Italian neighborhood hospital during the COVID-19 pandemic.

The novel SARS-CoV-2 pandemic arose in China in the late 2019 and soon after spread in the rest of the world. The management of SARS-CoV-2 is a serious challenge for all the healthcare professionals. The management of this disease has caused an epochal change in all of the hospitals. The surgical departments too were not excluded from management of COVID-19 patients, because of the disease itself, or as complication of surgical procedure. The surgeons too had to quickly adapt their skills, in order to recognize and treat this life-threatening problem. In the meantime, the surgeons had to ensure continuity of the oncall availability for the emergency procedures, meanwhile the regular scheduled surgical activities were suspended. We present here our experience in a neighborhood hospital located in Milan, Italy.

Nicolau syndrome caused by non-steroidal anti-inflammatory drugs: Systematic literature review.

AIM: Intramuscular or, more rarely, local drug injection is occasionally followed by immediate local pain, livedoid skin lesions and, some days later, the development of ischemic lesions. This very uncommon but potentially severe reaction, termed Nicolau syndrome, is traditionally associated with bismuth and ß-lactam antimicrobials. The aim of this report was to review the literature associating Nicolau syndrome with the administration of non-steroidal anti-inflammatory drugs. METHODS: The National Library, Excerpta Medica, Web of Science and Cochrane library databases were used. RESULTS: Sixty-two cases (40 females and 22 males aged from 13 to 81, median 57 years) of Nicolau syndrome were published after 1992. Fifty-three cases occurred after diclofenac. The remaining nine cases were associated with ketoprofen (N = 2), ketorolac (N = 2), phenylbutazone (N = 2), etofenamate (N = 1), ibuprofen (N = 1) and piroxicam (N = 1). CONCLUSION: Although Nicolau syndrome is extremely uncommon, physicians must be aware of this complication after intramuscular administration of non-steroidal anti-inflammatory drugs and should avoid unnecessary injections.

Altered regional brain T2 relaxation times in individuals with chronic orofacial neuropathic pain.

The neural mechanisms underlying the development and maintenance of chronic pain following nerve injury remain unclear. There is growing evidence that chronic neuropathic pain is associated with altered thalamic firing patterns, thalamocortical dysrhythmia and altered infra-slow oscillations in ascending pain pathways. Preclinical and post-mortem human studies have revealed that neuropathic pain is associated with prolonged astrocyte activation in the dorsal horn and we have suggested that this may result in altered gliotransmission, which results in altered resting neural rhythm in the ascending pain pathway. Evidence of astrocyte activation above the level of the dorsal horn in living humans is lacking and direct measurement of astrocyte activation in living humans is not possible, however, there is evidence that regional alterations in T2 relaxation times are indicative of astrogliosis. The aim of this study was to use T2 relaxometry to explore regional brain anatomy of the ascending pain pathway in individuals with chronic orofacial neuropathic pain. We found that in individuals with trigeminal neuropathic pain, decreases in T2 relaxation times occurred in the region of the spinal trigeminal nucleus and primary somatosensory cortex, as well as in higher order processing regions such as the dorsolateral prefrontal, cingulate and hippocampal/parahippocampal cortices. We speculate that these regional changes in T2 relaxation times reflect prolonged astrocyte activation, which results in altered brain rhythm and ultimately the constant perception of pain. Blocking prolonged astrocyte activation may be effective in preventing and even reversing the development of chronic pain following neural injury.

Disruption of default mode network dynamics in acute and chronic pain states.

It has been proposed that pain competes with other attention-demanding stimuli for cognitive resources, and many chronic pain patients display significant attention and mental flexibility deficits. These alterations may result from disruptions in the functioning of the default mode network (DMN) which plays a critical role in attention, memory, prospection and self-processing, and recent investigations have found alterations in DMN function in multiple chronic pain conditions. Whilst it has been proposed that these DMN alterations are a characteristic of pain that is chronic in nature, we recently reported altered oscillatory activity in the DMN during an acute, 5  minute noxious stimulus in healthy control subjects. We therefore hypothesize that altered DMN activity patterns will not be restricted to those in chronic pain but instead will also occur in healthy individuals during tonic noxious stimuli. We used functional magnetic resonance imaging to measure resting state infra-slow oscillatory activity and functional connectivity in patients with chronic orofacial pain at rest and in healthy controls during a 20-minute tonic pain stimulus. We found decreases in oscillatory activity in key regions of the DMN in patients with chronic pain, as well as in healthy controls during tonic pain in addition to changes in functional connectivity between the posterior cingulate cortex and areas of the DMN in both groups. The results show that similar alterations in DMN function occur in healthy individuals during acute noxious stimuli as well as in individuals with chronic pain. These DMN changes may reflect the presence of pain per se and may underlie alterations in attentional processes that occur in the presence of pain.

Extensive Computed Tomography versus Limited Screening for Detection of Occult Cancer in Unprovoked Venous Thromboembolism: A Multicenter, Controlled, Randomized Clinical Trial.

Patients with unprovoked venous thromboembolism (VTE) may harbor occult cancer. Whether an extensive diagnostic work-up for cancer has additional value over a more limited screening for detection of underlying malignancy in these patients is controversial. We performed a randomized multicenter trial to assess if in patients with unprovoked VTE, a computed tomography (CT)-based diagnostic strategy including thoracic, abdominal, and pelvic CT in combination with fecal occult blood test yields a higher cancer detection rate than a nonstandardized testing approach based on physicians' clinical judgment and patients' preferences. Cancer-free patients were followed up for up to 24 months. Of the 195 consecutive patients with unprovoked VTE who were eligible for this investigation, an occult cancer was identified in 10 of the 98 patients (10.2%) randomized to the CT-based strategy, and in 8 of the 97 (8.2%) allocated to the personalized strategy (absolute difference, 2.0%; 95% confidence interval, -7.2-11.1; p = 0.81). During follow-up, cancer was identified in an additional 2 patients in each group. Overall, 7 (7.1%) patients of the CT-based strategy died, as compared with 11 (11.3%) of the personalized strategy, with 2 and 4, respectively, due to cancer. In conclusion, a CT-based strategy in combination with fecal occult blood test does not provide a clinically significant benefit over more limited cancer screening for detecting occult cancer in patients with unprovoked VTE. (ClinicalTrials.gov number, NCT00361647).

Peritonectomy and hyperthermic intraperitoneal chemotherapy: cost analysis and sustainability.

BACKGROUND: Malignancies of the peritoneum remain a challenge in any hospital that accepts to manage them, due not only to difficulties associated with the complexity of the procedures involved but also the costs, which - in Italy and other countries that use a diagnosis-related group (DRG) system - are not adequately reimbursed. MATERIAL AND METHODS: We analyzed data relative to 24 patients operated on between September 2010 and May 2013 with special regard to operating room expenditure, ICU stay, duration of hospitalization, and DRG reimbursement. The total costs per patient included clinical, operating room, procedure, pathology, imaging, ward care, allied healthcare, pharmaceutical, and ICU costs. RESULTS: Postoperative hospital stay, drugs and materials, and operating room occupancy were the main factors affecting the expenditure for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We had a median hospitalization of 14 days, median ICU stay of 2.4 days, and median operating room occupancy of 585 min. The median expenditure for each case was € 21,744; the median reimbursement by the national health system € 8,375. CONCLUSIONS: In a DRG reimbursement system, the economic effort in the management of patients undergoing peritonectomy procedures may not be counterbalanced by adequate reimbursement. Joint efforts between medical and administration parties are mandatory to develop appropriate treatment protocols and keep down the costs.

[Atheroembolism renal disease: diagnosis and etiologic factors]. / La malattia renale ateroembolica: diagnosi ed eziologia.

Atheromatous renal disease is the major cause of renal insufficiency in the elderly, and cholesterol embolism is a manifestation of this disease. Cholesterol embolism occurs in patients suffering from diffuse erosive atherosclerosis, usually after triggering causes, such as aortic surgery, arterial invasive procedures (angiography, left heart catheterization and coronary angioplasty) and anticoagulant or thrombolytic therapy. It is characterized by occlusion of small arteries with cholesterol emboli deriving from eroded atheromatous plaques of the aorta or large feeder arteries. The proximity of the kidneys to the abdominal aorta and the large renal blood supply make the kidney a frequent target organ for cholesterol atheroembolism. The exact incidence of atheroembolic renal disease (AERD) is not known. The reported incidence AERD varied in the literature because of the differences in study design and the different criteria used for making the diagnosis. Retrospective data derived from autopsy or biopsy studies may exaggerate the frequency by including many subclinical cases. Clinical observations that are based on a short duration of follow-up after an invasive vascular procedure and the infrequency of the confirmatory renal biopsies can lead to an underestimation of the true incidence of AERD. The initial signs and symptoms in patients diagnosed with cholesterol embolism were blue toes syndrome, livedo reticularis, gangrene, leg, toe or foot pain, abdominal pain and flank or back pain, gross haematuria, accelerated hypertension and renal failure. Cholesterol embolism may also be associated with fever, increased erythrocyte sedimentation rate and eosinophilia. Thus, in the cases of spontaneous cholesterol embolism, differential diagnosis includes, polyarteritis nodosa, allergic vasculitis and subacute bacterial endocarditis. Skin and renal biopsy specimens are the best sample for histologic diagnosis. There is, at present, no pharmacological treatments shown to be effective in altering the course of the disease. Management is limited to supportive therapy and avoidance of anticoagulation; aortic procedures should be postponed.

Clinical significance and treatment of skin rash from erlotinib in non-small cell lung cancer patients: results of an Experts Panel Meeting.

Advances in the knowledge of tumor biology and mechanisms of oncogenesis has granted the singling out of several molecular targets for non-small cell lung cancer (NSCLC) treatment. Among these targets, epidermal growth factor receptor (EGFR), or HER1, has received particular attention in lung cancer treatment. Erlotinib, an orally available inhibitor of EGFR tyrosine kinase in a phase III randomized placebo-controlled trial (BR.21), has been proven to prolong survival in NSCLC patients after first or second line chemotherapy. Skin rash is the most common adverse event associated with erlotinib treatment and it is often cause of negative impact on patients' quality of life. There is no specific treatment for this toxicity due to the lack of evidence-based data and recommendations. A panel of Italian oncologists, who had participated to clinical trials and to the Expanded Access Program for erlotinib in NSCLC treatment, and dermatologists with experience with cutaneous toxicity from EGFR inhibitors, attended a Meeting held in Rome on December 2006 to discuss skin rash from erlotinib and to provide suggestions for managing this frequent side-effect.

Staphylococcus aureus bacteremia in patients with hematologic malignancies: a retrospective case-control study.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus bacteremia (SAB) continues to be a major problem related to both community and nosocomially acquired infection. Nevertheless few data are presently available in literature about this infection in patients with hematologic malignancies. DESIGN AND METHODS: The purpose of this retrospective study was to report further data on the clinical characteristics and outcome of patients with SAB. All episodes of SAB occurring between January 1997 and June 2001 were identified and defined by analysis of the patients' clinical records. RESULTS: The nosocomial mortality rate was only 3.5% and no patient developed secondary complications. Comparison between neutropenic hematologic patients with SAB and neutropenic hematologic patients with Gram-negative bacteremia (GNB) revealed an higher mortality in the latter group (p=0.03); furthermore, severe sepsis and septic shock were more frequent in patients with GNB (p<0.001). Comparison between neutropenic patients with hematologic malignancies and non-neutropenic ones with other underlying diseases revealed significantly higher morbidity and mortality rates in the latter group. Non neutropenic patients seemed to be more susceptible to both early complications, such as severe sepsis or septic shock (p=0.002) and to later ones, such as endocarditis and metastatic abscesses (p=0.02). INTERPRETATION AND CONCLUSIONS: Our results seem to suggest that SAB in patients with hematologic malignancies is often a low inoculum infection associated with negligible morbidity and mortality rates, especially when adequate antistaphylococcal therapy is administered promptly.

USS internal fixator in lumbar and thoracolumbar vertebral fractures.

The authors report their experience in the surgical treatment of lumbar and thoracolumbar vertebral fractures with the use of the USS-AO internal fixator at the Division of Orthopaedics of the Azienda Ospedaliera OO.RR. in Foggia between July 1996 and July 1998. The cases, although not numerous, confirm the effectiveness of the method of correction and its maintenance even in time.

Detection of two forms of HBeAg (free-and IgG-bound HBeAg) in patients with HBe antigenemia using staphylococcus bearing protein A.

Protein A-bearing Staphylococcus aureus organisms (STA) were used to separate free HBeAg from IgG-bound HBeAg. Free HBeAg was detected in the supernate while IgG-bound HBeAg could be liberated from the pellets using MgCl2 or a glycine buffer. HBeAg was determined by radioimmunoassay and the results expressed as patient's cpm/normal control's cpm ratio (S/N ratio). This ratio was demonstrated to be proportionate to the antigen concentration and used as a titer of HBeAg. Sera of 40 HBsAg-negative healthy volunteers and 82 HBeAg-positive patients who were either asymptomatic HBsAg carriers or had various diseases including chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), and renal disease undergoing hemodialysis, were tested for free HBeAg and IgG-bound HBeAg. Patients with CAH from two different countries were compared. Free HBeAg was detected in all patients but one, IgG-bound HBeAg was detected with similar prevalences (from 56% to 67%) in HBsAg asymptomatic carriers, hemodialysis patients, CPH and Italian CAH patients. In contrast, all CAH patients from New York, who had frequently been exposed to HBV infection, had detectable levels of IgG-bound HBeAg, with the highest S/N ratios observed in the study, and frequently showed an unfavorable outcome. In AVH due to HBV and delta agent co-infection, IgG-bound HBeAg was detected in two of four patients only in the initial stage of the disease. The data reported indicate that a separate determination of free- and IgG-bound HBeAg may have clinical value.