Secondary bacterial infections & extensively drug-resistant bacteria among COVID-19 hospitalized patients at the University Hospital in Kraków.

INTRODUCTION: Healthcare-associated infections (HAI) and bacterial antimicrobial resistance posed a therapeutic risk during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to analyze the HAIs in COVID-19 patients in the Intensive Care Unit (ICU) and non-ICU at the University Hospital in Krakow (UHK) with an emphasis on the susceptibility of the most frequently isolated pathogens and the prevalence of extensively drug resistant (XDR) microorganisms. METHODS: This laboratory-based study was carried out at the University Hospital in Krakow in the ICU and non-ICUs dedicated to COVID-19 patients between May 2021 and January 2022. All isolates of Klebsiella pneumoniae were analyzed using PFGE protocol. RESULTS: 292 independent HAI cases were identified, with the predominance of urinary tract infections (UTI), especially in the non-ICU setting. The most common ICU syndrome was pneumonia (PNA). The prevalence of XDR organisms was 22.6% in the ICU and 14.8% in non-ICUs among all isolates. The incidence of carbapenem-resistant Enterobacteriaceae infection was 24.8 cases per 10,000 hospitalizations and the carbapenem-resistant A. baumannii infection incidence was 208.8 cases per 10,000 hospitalizations. The prevalence of XDR strains was highest in Acinetobacter spp, in PNA cases. The PFGE typing demonstrated that almost all XDR strains varied widely from each other. CONCLUSIONS: In this study, there was a high incidence of HAI in COVID-19 patients, especially when compared to Western Europe and the United States. Similarly, the prevalence of XDR microorganisms, especially XDR-A.baumannii, was also high. PFGE did not confirm the horizontal spread of any organism strains.

Topical clonidine for neuropathic pain in adults.

BACKGROUND: Clonidine is a presynaptic alpha-2-adrenergic receptor agonist that has been used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs has been gaining interest since the beginning of the century, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated for almost 20 years in clinical trials. This is an update of the original Cochrane Review published in Issue 8, 2015. OBJECTIVES: The objective of this review was to assess the analgesic efficacy and safety of TC compared with placebo or other drugs in adults aged 18 years or above with chronic neuropathic pain. SEARCH METHODS: For this update we searched the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid), and Embase (Ovid) databases, and reference lists of retrieved papers and trial registries. We also contacted experts in the field. The most recent search was performed on 27 October 2021. SELECTION CRITERIA: We included randomised, double-blind studies of at least two weeks' duration comparing TC versus placebo or other active treatment in adults with chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references for eligibility, extracted data, and assessed risk of bias. Any discrepancies were resolved by discussion or by consulting a third review author if necessary. Where required, we contacted trial authors to request additional information. We presented pooled estimates for dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) with P values. We used Review Manager Web software to perform the meta-analyses. We used a fixed-effect model if we considered heterogeneity as not important; otherwise, we used a random-effects model.  The review primary outcomes were: participant-reported pain relief of 50% or greater; participant-reported pain relief of 30% or greater; much or very much improved on Patient Global Impression of Change scale (PGIC); and very much improved on PGIC. Secondary outcomes included withdrawals due to adverse events; participants experiencing at least one adverse event; and withdrawals due to lack of efficacy. All outcomes were measured at the longest follow-up period. We assessed the certainty of evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We included four studies in the review (two new in this update), with a total of 743 participants with painful diabetic neuropathy (PDN). TC (0.1% or 0.2%) was applied in gel form to the painful area two to three times daily. The double-blind treatment phase of three studies lasted 8 weeks to 85 days and compared TC versus placebo. In the fourth study, the double-blind treatment phase lasted 12 weeks and compared TC versus topical capsaicin. We assessed the studies as at unclear or high risk of bias for most domains; all studies were at unclear risk of bias for allocation concealment and blinding of outcome assessment; one study was at high risk of bias for blinding of participants and personnel; two studies were at high risk of attrition bias; and three studies were at high risk of bias due to notable funding concerns. We judged the certainty of evidence (GRADE) to be moderate to very low, downgrading for study limitations, imprecision of results, and publication bias. TC compared to placebo There was no evidence of a difference in number of participants with participant-reported pain relief of 50% or greater during longest follow-up period (12 weeks) between groups (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.78 to 1.86; 179 participants; 1 study; low certainty evidence). However, the number of participants with participant-reported pain relief of 30% or greater during longest follow-up period (8 to 12 weeks) was higher in the TC group compared with placebo (RR 1.35, 95% CI 1.03 to 1.77; 344 participants; 2 studies, very low certainty evidence). The number needed to treat for an additional beneficial outcome (NNTB) for this comparison was 8.33 (95% CI 4.3 to 50.0). Also, there was no evidence of a difference between groups for the outcomes much or very much improved on the PGIC during longest follow-up period (12 weeks) or very much improved on PGIC during the longest follow-up period (12 weeks) (RR 1.06, 95% CI 0.76 to 1.49 and RR 1.82, 95% CI 0.89 to 3.72, respectively; 179 participants; 1 study; low certainty evidence). We observed no evidence of a difference between groups in withdrawals due to adverse events and withdrawals due to lack of efficacy during the longest follow-up period (12 weeks) (RR 0.34, 95% CI 0.04 to 3.18 and RR 1.01, 95% CI 0.06 to 15.92, respectively; 179 participants; 1 study; low certainty evidence) and participants experiencing at least one adverse event during longest follow-up period (12 weeks) (RR 0.65, 95% CI 0.14 to 3.05; 344 participants; 2 studies; low certainty evidence).  TC compared to active comparator There was no evidence of a difference in the number of participants with participant-reported pain relief of 50% or greater during longest follow-up period (12 weeks) between groups (RR 1.41, 95% CI 0.99 to 2.0; 139 participants; 1 study; low certainty evidence). Other outcomes were not reported. AUTHORS' CONCLUSIONS: This is an update of a review published in 2015, for which our conclusions remain unchanged. Topical clonidine may provide some benefit to adults with painful diabetic neuropathy; however, the evidence is very uncertain. Additional trials are needed to assess TC in other neuropathic pain conditions and to determine whether it is possible to predict who or which groups of people will benefit from TC.

The frequency and risk factors for surgery dissatisfaction in patients undergoing lumbar or cervical surgery for degenerative spinal conditions.

This study evaluated the frequency and risk factors for surgery dissatisfaction in patients undergoing lumbar or cervical surgery for degenerative spinal conditions. Based on the Patient Satisfaction Index (PSI) at 6 months after surgery, we divided patients into two groups: a satisfied and a dissatisfied group. We evaluated the association between patient dissatisfaction and five categories of variables:1) sociodemographic; 2) preoperative pain and disability [pain duration, level of surgery, previous spinal surgeries, pain scores as measured by the Short Form McGill Pain Questionnaire (SF-MPQ), numerical rating of average pain (NRS), disability as measured by the Oswestry Disability Index (ODI)]; 3) preoperative psychological status [depression, anxiety, and overall distress as measured by the Hospital Anxiety and Depression Scale (HADS), life satisfaction as measured by the Satisfaction With Life Scale (SWLS), and surgery expectations (SE) as measured by a Likert scale]; 4) postoperative improvements in pain and disability [improvements in SF-MPQ, improvement in ODI] and 5) postoperative psychological status [HADS, SWLS]. Results showed that 17.8% patients were dissatisfied with surgery. In the multivariate logistic analysis, more negative surgery expectations, smaller improvement in ODI scores, and a greater postoperative overall distress were significant risk factors associated with patient dissatisfaction with surgery.

The role of complementary and alternative methods in the treatment of pain in patients with cancer - current evidence and clinical practice: a narrative review.

INTRODUCTION: Pain related to cancer, despite the numerous treatment options available, is still a challenge in contemporary pain medicine. The unsatisfactory treatment of cancer pain is one of the main reasons why patients seek complementary and alternative methods (CAM) and a more integrative/holistic approach to pain management. The popularity of CAM forces healthcare professionals to provide patients with current and evidence-based information on the effectiveness and safety of CAM. The aim of the paper is to present current evidence and limitations regarding CAM commonly used in the pain management of cancer patients. MATERIAL AND METHODS: The paper comprehensively reviews the current and most relevant literature considering the integrative approach to management of pain due to cancer disease and/or cancer treatment. RESULTS: The available data from clinical trials, meta-analyses, and systematic reviews supports the effectiveness of acupuncture, massage, physical exercises, music therapy, and mind-body therapies as adjunct therapies for alleviating pain in cancer patients, although the supporting evidence is weak or moderate. CONCLUSIONS: Based on the available knowledge, physicians should be capable of advising the cancer patient as to which CAM methods can be used safely, which are contraindicated, and what therapeutic effects they may expect, especially when standard pain treatment fails or induces serious side effects. An integrative approach to cancer pain management may improve the quality of pain treatment, patients' quality of life, and satisfaction with pain relief.

Perioperative restrictive versus goal-directed fluid therapy for adults undergoing major non-cardiac surgery.

BACKGROUND: Perioperative fluid management is a crucial element of perioperative care and has been studied extensively recently; however, 'the right amount' remains uncertain. One concept in perioperative fluid handling is goal-directed fluid therapy (GDFT), wherein fluid administration targets various continuously measured haemodynamic variables with the aim of optimizing oxygen delivery. Another recently raised concept is that perioperative restrictive fluid therapy (RFT) may be beneficial and at least as effective as GDFT, with lower cost and less resource utilization. OBJECTIVES: To investigate whether RFT may be more beneficial than GDFT for adults undergoing major non-cardiac surgery. SEARCH METHODS: We searched the following electronic databases on 11 October 2019: Cochrane Central Register of Controlled Trials, in the Cochrane Libary; MEDLINE; and Embase. Additionally, we performed a targeted search in Google Scholar and searched trial registries (World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov) for ongoing and unpublished trials. We scanned the reference lists and citations of included trials and any relevant systematic reviews identified. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing perioperative RFT versus GDFT for adults (aged ≥ 18 years) undergoing major non-cardiac surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references for eligibility, extracted data, and assessed risk of bias. We resolved discrepancies by discussion and consulted a third review author if necessary. When necessary, we contacted trial authors to request additional information. We presented pooled estimates for dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), and for continuous outcomes as mean differences (MDs) with standard deviations (SDs). We used Review Manager 5 software to perform the meta-analyses. We used a fixed-effect model if we considered heterogeneity as not important; otherwise, we used a random-effects model. We used Poisson regression models to compare the average number of complications per person. MAIN RESULTS: From 6396 citations, we included six studies with a total of 562 participants. Five studies were performed in participants undergoing abdominal surgery (including one study in participants undergoing cytoreductive abdominal surgery with hyperthermic intraperitoneal chemotherapy (HIPEC)), and one study was performed in participants undergoing orthopaedic surgery. In all studies, surgeries were elective. In five studies, crystalloids were used for basal infusion and colloids for boluses, and in one study, colloid was used for both basal infusion and boluses. Five studies reported the ASA (American Society of Anesthesiologists) status of participants. Most participants were ASA II (60.4%), 22.7% were ASA I, and only 16.9% were ASA III. No study participants were ASA IV. For the GDFT group, oesophageal doppler monitoring was used in three studies, uncalibrated invasive arterial pressure analysis systems in two studies, and a non-invasive arterial pressure monitoring system in one study. In all studies, GDFT optimization was conducted only intraoperatively. Only one study was at low risk of bias in all domains. The other five studies were at unclear or high risk of bias in one to three domains. RFT may have no effect on the rate of major complications compared to GDFT, but the evidence is very uncertain (RR 1.61, 95% CI 0.78 to 3.34; 484 participants; 5 studies; very low-certainty evidence). RFT may increase the risk of all-cause mortality compared to GDFT, but the evidence on this is also very uncertain (RD 0.03, 95% CI 0.00 to 0.06; 544 participants; 6 studies; very low-certainty evidence). In a post-hoc analysis using a Peto odds ratio (OR) or a Poisson regression model, the odds of all-cause mortality were 4.81 times greater with the use of RFT compared to GDFT, but the evidence again is very uncertain (Peto OR 4.81, 95% CI 1.38 to 16.84; 544 participants; 6 studies; very low-certainty evidence). Nevertheless, sensitivity analysis shows that exclusion of a study in which the final volume of fluid received intraoperatively was higher in the RFT group than in the GDFT group revealed no differences in mortality. Based on analysis of secondary outcomes, such as length of hospital stay (464 participants; 5 studies; very low-certainty evidence), surgery-related complications (364 participants; 4 studies; very low-certainty evidence), non-surgery-related complications (74 participants; 1 study; very low-certainty evidence), renal failure (410 participants; 4 studies; very low-certainty evidence), and quality of surgical recovery (74 participants; 1 study; very low-certainty evidence), GDFT may have no effect on the risk of these outcomes compared to RFT, but the evidence is very uncertain. Included studies provided no data on administration of vasopressors or inotropes to correct haemodynamic instability nor on cost of treatment. AUTHORS' CONCLUSIONS: Based on very low-certainty evidence, we are uncertain whether RFT is inferior to GDFT in selected populations of adults undergoing major non-cardiac surgery. The evidence is based mainly on data from studies on abdominal surgery in a low-risk population. The evidence does not address higher-risk populations or other surgery types. Larger, higher-quality RCTs including a wider spectrum of surgery types and a wider spectrum of patient groups, including high-risk populations, are needed to determine effects of the intervention.

Prevalence of Chronic Pain, Particularly with Neuropathic Component, and Its Effect on Overall Functioning of Elderly Patients.

BACKGROUND The prevalence of chronic pain among the elderly is high (estimated at 25-85%) and may adversely affect their everyday functioning, although it is often unrecognized. MATERIAL AND METHODS The aim of this study was to assess the prevalence of chronic pain, especially with the neuropathic component, and its effect on overall functioning of elderly patients. We enrolled 145 subjects older than 60 years (nursing home residents, or patients of outpatient geriatric clinic). Information on co-morbidities, functional and mental status, and medications was obtained using a questionnaire. Chronic pain was defined as lasting >3 months and the presence of neuropathic component was detected using the DN4 Questionnaire (Douleur Neuropathique en Questions). RESULTS The mean age of patients was 76±9.68 years. Chronic pain was reported by 78% of participants and 32% reported neuropathic pain with neuropathic component (DN4 score ≥4 points). Patients complaining of chronic pain significantly more often presented mood disorders and lower satisfaction with life (particularly those with the highest pain intensity), with no difference in functional status according to the ADL (Activities of Daily Living) tool. Participants with chronic pain were treated with paracetamol (45%), non-steroidal anti-inflammatory drugs (25%), and opioids (24%). CONCLUSIONS The prevalence of chronic pain, particularly with neuropathic component, in the elderly population seems to be higher than expected based on previous reports, and its treatment appears to be ineffective. This problem requires further research and dissemination of knowledge on the diagnosis and treatment of chronic pain among health care workers caring for elderly patients on a daily basis.

Bone Pain in Cancer Patients: Mechanisms and Current Treatment.

The skeletal system is the third most common site for cancer metastases, surpassed only by the lungs and liver. Many tumors, especially those of the breast, prostate, lungs, and kidneys, have a strong predilection to metastasize to bone, which causes pain, hypercalcemia, pathological skeletal fractures, compression of the spinal cord or other nervous structures, decreased mobility, and increased mortality. Metastatic cancer-induced bone pain (CIBP) is a type of chronic pain with unique and complex pathophysiology characterized by nociceptive and neuropathic components. Its treatment should be multimodal (pharmacological and non-pharmacological), including causal anticancer and symptomatic analgesic treatment to improve quality of life (QoL). The aim of this paper is to discuss the mechanisms involved in the occurrence and persistence of cancer-associated bone pain and to review the treatment methods recommended by experts in clinical practice. The final part of the paper reviews experimental therapeutic methods that are currently being studied and that may improve the efficacy of bone pain treatment in cancer patients in the future.

Mechanisms of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating this syndrome are very limited. There are six main substance groups that cause damage to peripheral sensory, motor and autonomic neurons, which result in the development of CIPN: platinum-based antineoplastic agents, vinca alkaloids, epothilones (ixabepilone), taxanes, proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide). Among them, the most neurotoxic are platinum-based agents, taxanes, ixabepilone and thalidomide; other less neurotoxic but also commonlyused drugs are bortezomib and vinca alkaloids. This paper reviews the clinical picture of CIPN and the neurotoxicity mechanisms of the most common antineoplastic agents. A better understanding of the risk factors and underlying mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies.

Transdermal and Topical Drug Administration in the Treatment of Pain.

The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients' age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non-steroidal anti-inflammatory drugs (NSAIDs) applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti-inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline) act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

[The impact of the type of anesthesia on postoperative pain after surgical correction of hallux valgus deformity]. / Oddzialywanie rodzaju znieczulenia na stopien nasilenia bólu pooperacyjnego po korekcji operacyjnej deformacji koslawej palucha.

BACKGROUND: Different kind of anesthesia are used in hallux valgus surgery e.g general and spinal anesthesia, peripheral blocks (sciatic, femoral, ankle), patient controlled analgesia (PCA), multimodal anesthesia and preemptive local anesthesia. The type of anesthesia can play a key role in postoperative pain control. The aim of the study was to compare the effectiveness of different types of anesthesia in reduction of postoperative pain. MATERIAL AND METHODS: In the years 2009-2015,260 hallux valgus surgeries were performed using chevron, scarf, Mitchell-Kramer or Kramer method. Depending on the kind of anesthesia, patients were assigned to one of the five groups: group A--general, group B--spinal, group C--general with local preemptive, group D--spinal with local preemptive, group E--sciatic (popliteal) block. The level of postoperative pain intensity was measured using a visual analogue scale (VAS) in 2, 4, 8, 12, 16, 24, 48 and 72 hours after surgery. Regardless of the type of anesthesia each patient received three doses of 1000 mg paracetamol, two doses of 100 mg ketoprofen and at the request 7.5 mg morphine sulphate intravenously. During discharge from the hospital followed a day after surgery each patient received a prescription for 325 mg paracetamol + 37.5 mg tramadol hydrochloride . All adverse effects of anesthesia and drugs were reported. RESULTS: During the first 24 hours average pain intensity measured by VAS was increased in group A compared to others (p < 0.05). Between 8 and 24 hours, a similar relationship was observed in group B compared to C, D and E (p < 0.05). At the second and third day after surgery the differences in VAS were not statistically significant. In groups C, D and E we observed decreased use of 7.5 mg morphine sulphate on demand and 325 mg paracetamol + 37.5 mg tramadol hydrochloride. In two patients of group A and one in group B dizziness and nausea after use of 325 mg paracetamol + 37.5 mg of tramadol hydrochloride were noted. Two patients in group B and one of group D had incident of bradycardia. Three patients of group A and C had nausea and vomiting. We did not observe side effects of injected solution of local anesthetics. CONCLUSIONS: Preemptive local anesthetic infiltration combined with general or spinal anesthesia and sciatic (popliteal) block are more effective than isolated general and spinal anesthesia in reducing the level of postoperative pain after hallux valgus surgery. They are also associated with decreased number of complications and reduction of applied analgesics.

[Effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn I-Shot) in the treatment of knee osteoarthritis]. / Skutecznosc dzialania i bezpieczenstwo preparatu Suplasyn 1-Shot w leczeniu choroby zwyrodnieniowej stawów kolanowych.

Osteoarthritis (OA) is one of the leading causes of disability in the elderly. The changes in the lubricating properties of synovial fluid lead to significant pain and loss of function. Viscosupplementation, in which hyaluronic acid (HA) is injected into the knee joint, has evolved into an important part of our current therapeutic regimen in addressing the patient with knee pain due to OA. Intra-articular HA has proven to be an effective, safe, and tolerable treatment for symptomatic knee OA. In an effort to limit cardiovascular, gastrointestinal and renal safety concerns with COX-2 selective and nonselective NSAIDs and maximize HA efficacy, it is even proposed using HA earlier in the treatment paradigm for knee OA and also as part of a comprehensive treatment strategy. Our study reconfirmed effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn) in the treatment of knee osteoarthritis.

Topical clonidine for neuropathic pain.

BACKGROUND: Clonidine is a presynaptic alpha-2-adrenergic receptor agonist used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs is currently gaining interest, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated recently in clinical trials. OBJECTIVES: The objectives of this review were to assess the analgesic efficacy of TC for chronic neuropathic pain in adults and to assess the frequency of adverse events associated with clinical use of TC for chronic neuropathic pain. SEARCH METHODS: We searched the Cochrane Register of Studies (CRS) Online (Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE and EMBASE databases, reference lists of retrieved papers and trial registries, and we contacted experts in the field. We performed the most recent search on 17 September 2014. SELECTION CRITERIA: We included randomised, double-blind studies of at least two weeks' duration comparing TC versus placebo or other active treatment in patients with chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors extracted data from the studies and assessed bias. We planned three tiers of evidence analysis. The first tier was designed to analyse data meeting current best standards, by which studies reported the outcome of at least 50% pain intensity reduction over baseline (or its equivalent) without use of the last observation carried forward or other imputation method for dropouts, reported an intention-to-treat (ITT) analysis, lasted eight weeks or longer, had a parallel-group design and included at least 200 participants (preferably at least 400) in the comparison. The second tier was designed to use data from at least 200 participants but in cases in which one of the above conditions was not met. The third tier of evidence was assumed in other situations. MAIN RESULTS: We included two studies in the review, with a total of 344 participants. Studies lasted 8 weeks and 12 weeks and compared TC versus placebo. 0.1%. TC was applied in gel form to the painful area two to three times daily.Studies included in this review were subject to potential bias and were classified as of moderate or low quality. One drug manufacturer supported both studies.We found no top-tier evidence for TC in neuropathic pain. Second-tier evidence indicated slight improvement after the drug was used in study participants with painful diabetic neuropathy (PDN). A greater number of participants in the TC group had at least 30% reduction in pain compared with placebo (risk ratio (RR) 1.35, 95% confidence interval (CI) 1.03 to 1.77; number needed to treat for an additional beneficial outcome (NNTB) 8.33, 95% CI 4.3 to 50). Third-tier evidence indicated that TC was no better than placebo for achieving at least 50% reduction in pain intensity and on the Patient Global Impression of Change Scale. The two included studies could be subject to significant bias. We found no studies that reported other neuropathic pain conditions.The rate of adverse events did not differ between groups, with the exception of a higher incidence of mild skin reactions in the placebo group, which should have no clinical significance. AUTHORS' CONCLUSIONS: Limited evidence from a small number of studies of moderate to low quality suggests that TC may provide some benefit in peripheral diabetic neuropathy. The drug may be useful in situations for which no better treatment options are available because of lack of efficacy, contraindications or adverse events. Additional trials are needed to assess TC in other neuropathic pain conditions and to determine how patients who have a chance to respond to the drug should be selected for treatment.

Diagnosis and management of neuropathic pain: review of literature and recommendations of the Polish Association for the Study of Pain and the Polish Neurological Society - Part Two.

Neuropathic pain may be caused by a variety of lesions or diseases of both the peripheral and central nervous system. The most common and best known syndromes of peripheral neuropathic pain are painful diabetic neuropathy, trigeminal and post-herpetic neuralgia, persistent post-operative and post-traumatic pain, complex regional pain syndrome, cancer-related neuropathic pain, HIV-related neuropathic pain and pain after amputation. The less common central pain comprises primarily central post-stroke pain, pain after spinal cord injury, central pain in Parkinson disease or in other neurodegenerative diseases, pain in syringomyelia and in multiple sclerosis. A multidisciplinary team of Polish experts, commissioned by the Polish Association for the Study of Pain and the Polish Neurological Society, has reviewed the literature on various types of neuropathic pain, with special focus on the available international guidelines, and has formulated recommendations on their diagnosis and treatment, in accordance with the principles of evidence-based medicine (EBM). High quality studies on the efficacy of various medicines and medical procedures in many neuropathic pain syndromes are scarce, which makes the recommendations less robust.

Diagnosis and management of neuropathic pain: review of literature and recommendations of the Polish Association for the study of pain and the Polish Neurological Society - part one.

Neuropathic pain still present a major diagnostic and therapeutic challenge despite considerable progress in understanding of its mechanisms and publication of number of studies which assessed the efficacy and safety of drugs used in the symptomatic treatment. In practice, it is diagnosed less frequently than recognised in the epidemiological studies, and many patients do not achieve satisfactory outcomes of treatment. A multidisciplinary team of Polish experts, commissioned by the Polish Association for the Study of Pain and the Polish Neurological Society, has reviewed the literature on neuropathic pain, with special focus on the published international recommendations, and formulated recommendations on neuropathic pain diagnosis and treatment, in accordance with the principles of evidence-based medicine. The paper presents also background information on the neuropathic pain definition, epidemiology, pathomechanism and method of assessment. The diagnosis of neuropathic pain may be established based on medical history and physical examination including special assessment of the somatosensory system. First-line drugs used in pharmacological management of neuropathic pain are: tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin, opioids and lidocaine patches.

COVID-19-Associated Pulmonary Aspergillosis in Intensive Care Unit Patients from Poland.

Coronavirus disease 2019 (COVID-19) has been shown to be a favoring factor for aspergillosis, especially in a severe course requiring admission to the intensive care unit (ICU). The aim of the study was to assess the morbidity of CAPA among ICU patients in Poland and to analyze applied diagnostic and therapeutic procedures. Medical documentation of patients hospitalized at the temporary COVID-19 dedicated ICU of the University Hospital in Krakow, Poland, from May 2021 to January 2022 was analyzed. In the analyzed period, 17 cases of CAPA were reported with an incidence density rate of 9 per 10 000 patient days and an incidence rate of 1%. Aspergillus fumigatus and Aspergillus niger were isolated from lower respiratory samples. Antifungal therapy was administered to 9 patients (52.9%). Seven patients (77.8%) received voriconazole. The CAPA fatality case rate was 76.5%. The results of the study indicate the need to increase the awareness of medical staff about the possibility of fungal co-infections in ICU patients with COVID-19 and to use the available diagnostic and therapeutic tools more effectively.

Mirogabalin Decreases Pain-like Behaviors by Inhibiting the Microglial/Macrophage Activation, p38MAPK Signaling, and Pronociceptive CCL2 and CCL5 Release in a Mouse Model of Neuropathic Pain.

Neuropathic pain is a chronic condition that significantly reduces the quality of life of many patients as a result of ineffective pain relief therapy. For that reason, looking for new analgesics remains an important issue. Mirogabalin is a new gabapentinoid that is a specific ligand for the α2σ-1 and α2σ-2 subunits of voltage-gated calcium channels. In the present study, we compared the analgesic effect of pregabalin and mirogabalin in a neuropathic pain chronic constriction injury (CCI) of the sciatic nerve in a mouse model. The main purpose of our study was to determine the effectiveness of mirogabalin administered both once and repeatedly and to explain how the drug influences highly activated cells at the spinal cord level in neuropathy. We also sought to understand whether mirogabalin modulates the selected intracellular pathways (p38MAPK, ERK, JNK) and chemokines (CCL2, CCL5) important for nociceptive transmission, which is crucial information from a clinical perspective. First, our study provides evidence that a single mirogabalin administration diminishes tactile hypersensitivity more effectively than pregabalin. Second, research shows that several indirect mechanisms may be responsible for the beneficial analgesic effect of mirogabalin. This study reports that repeated intraperitoneally (i.p.) mirogabalin administration strongly prevents spinal microglia/macrophage activation evoked by nerve injury, slightly suppresses astroglia and neutrophil infiltration, and reduces the p38MAPK levels associated with neuropathic pain, as measured on Day 7. Moreover, mirogabalin strongly diminished the levels of the pronociceptive chemokines CCL2 and CCL5. Our results indicate that mirogabalin may represent a new strategy for the effective pharmacotherapy of neuropathic pain.

Effects of vagus nerve stimulation in visceral pain model.

Visceral pain is an important therapeutic problem. A number of studies have established that abdominal vagal afferents modulate somatic pain behavior. Although it is not clear if vagal afferents transmit nociceptive information, a change in their activity can increase or decrease nociceptive transmission in visceral pain. Aims of the present study were to determine whether the subdiaphragmatic vagus nerves play a role in the endogenous pain inhibitory mechanisms in visceral pain model and whether it involves opioidergic pathways. Data obtained in our studies show that vagus nerve plays the direct role in conveying the nociceptive information in the peritonitis model of visceral pain. We have shown, that vagal afferents exhibit an increase in excitability and subdiaphragmatic vagotomy decrease nociceptive behavior in visceral pain in rats. We have also tested two different stimulation parameters of chronic subdiaphragmatic vagal nerve stimulation: VNS1 (high-intensity) and VNS2 (low-intensity) in visceral pain model in rats. Both stimulation parameters increased pain threshold but VNS1 was more effective than VNS2. Naloxone inhibited the antinociceptive effects of VNS, reversing partially increase in the pain threshold in rats and increases number of writhes in visceral pain model. Therefore, our data indicate that this analgesic effect of the VNS is mediated, at least in part, by descending opioidergic pathways. The present study has confirmed the importance of vagal afferents for nociception in general and proven that this role is not limited to somatic pain but also extends to visceral pain.

Pentoxifylline modifies central and peripheral vagal mechanism in acute and chronic pain models.

The inflammatory process gives the way to hyperalgesia that is documented by the animal experimental studies. Pentoxifylline (PTX) has strong antyinflamatory effects, decreases TNF-alpha and other proinflammatory cytokines production. Therefore, the aim of present investigation was to evaluate the effectiveness of PTX in nociception processes, especially in aspects of vagal activity, in experimental pain models: visceral pain (VP), neuropathy (CCI) and neurogenic inflammation (NI). In VP and CCI models we observed significant increase in the pain threshold after blocking proinflammatory cytokines whereas in NI there was no such effect. In our studies we also observed the increase of vagal afferents activity in VP and CCI, on the contrary to NI model. In summary, our study demonstrates that preemptive inhibition of proinflammatory cytokine synthesis by treatment with PTX is useful in antagonizing hyperalgesia in inflammatory pain. Pentoxifylline reduces central and peripheral sensitization processes depend on the vagal component in both acute and chronic pain models but in a different manner and mechanisms. Our results establish the participation of inflammatory and vagal component in nociception. The modulation of the vagal system offers the new possibilities of the pain treatment in patients resistant to the classical analgesic therapy.

Use of Continuous Veno-Venous Hemodialysis (CVVHD) in Treatment of a Polytrauma Patient with Severe Hemophilia A.

BACKGROUND There are very few reports in the literature worldwide on how to deliver continuous renal replacement therapy (CRRT) to patients with multi-organ trauma and severe hemophilia A. The aim of this case report is to describe successful multidisciplinary, intensive treatment of a patient with multi-organ trauma suffering from severe hemophilia A with the use of continuous veno-venous hemodialysis with regional citrate anticoagulation (Ci-Ca CVVHD). CASE REPORT We report a case of a 47-year-old man with severe hemophilia A, who had multi-organ trauma as a result of a serious traffic accident and was admitted to the Trauma Centre of Emergency and Disaster Medicine in Krakow, Poland in critical condition. Due to elevated laboratory markers of kidney damage (creatinine 204 mmol/l, glomerular filtration rate (GFR) 32 ml/min/1.73 m²), very high myoglobin level (>1000 µ/l) associated with rhabdomyolysis, oliguria (diuresis <0.5 ml/kg/h), and overhydration as a consequence of massive transfusion of blood products and fluids, on day 2 after the injury Ci-Ca CVVHD was initiated as a part of intensive, multidisciplinary treatment. This approach proved to be successful in our patient as he was discharged from the Intensive Care Unit on day 45 after the injury in good general condition, with stable circulatory and respiratory system, without any apparent neurological deficits, and with good renal function (creatinine 50 mmol/l, GFR >60 ml/min/1.73 m²). CONCLUSIONS Our case report shows that intensive, multidisciplinary treatment with implementation of Ci-Ca CVVHD may be an effective and safe method of care for patients with multi-organ trauma and hemophilia A.

Sudden Cardiac Arrest in a Patient With COVID-19 as a Result of Severe Hyperkalemia After Administration of Succinylcholine Chloride for Reintubation. A Case Report.

Background: We present a case study of a man with coronavirus disease 2019 (COVID-19) who developed cardiac arrest as a result of hyperkalemia following administration of chlororsuccinylcholine during endotracheal intubation. Case Summary: A patient with a severe course of COVID-19, hospitalized in the Intensive Care Unit, underwent reintubation on day 16. The applied scheme was rapid sequence induction and intubation with administration of chlororsuccinylcholine. Immediately after intubation, there was a sudden cardiac arrest due to hyperkalemia (cK + 10.2 meq/L). Treatment was initiated as per guidelines, which resulted in a return to spontaneous circulation after 6 min. Conclusion: Chlorsucynylcholine may cause life-threatening hyperkalemia. We recommend using rocuronium as a neuromuscular blocking agent in critically ill COVID-19 patients due to its more optimal safety profile.